<?xml version="1.0" encoding="US-ASCII"?>
<!-- Generated by CompSci Transform (tm) - http://www.compsciresources.com -->
<!-- Created: Mon Apr 15 20:24:45 UTC 2024 -->
<xs:schema elementFormDefault="qualified" xmlns:srt-types="http://fasb.org/srt-types/2023" targetNamespace="http://www.optimizerx.com/20231231" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:us-types="http://fasb.org/us-types/2023" xmlns:oprx="http://www.optimizerx.com/20231231" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xmlns:dtr="http://www.xbrl.org/dtr/type/2022-03-31" xmlns:xbrli="http://www.xbrl.org/2003/instance">
  <xs:annotation>
    <xs:appinfo>
      <link:linkbaseRef xlink:type="simple" xlink:href="oprx-20231231_lab.xml" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:role="http://www.xbrl.org/2003/role/labelLinkbaseRef"/>
      <link:linkbaseRef xlink:type="simple" xlink:href="oprx-20231231_pre.xml" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:role="http://www.xbrl.org/2003/role/presentationLinkbaseRef"/>
      <link:linkbaseRef xlink:type="simple" xlink:href="oprx-20231231_def.xml" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:role="http://www.xbrl.org/2003/role/definitionLinkbaseRef"/>
      <link:linkbaseRef xlink:type="simple" xlink:href="oprx-20231231_cal.xml" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:role="http://www.xbrl.org/2003/role/calculationLinkbaseRef"/>
      <link:roleType roleURI="http://www.optimizerx.com/role/ConsolidatedBalanceSheet" id="oprx_r_ConsolidatedBalanceSheet">
        <link:definition>995301 - Statement - Consolidated Balance Sheets</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ConsolidatedBalanceSheet_Parentheticals" id="oprx_r_ConsolidatedBalanceSheet_Parentheticals">
        <link:definition>995302 - Statement - Consolidated Balance Sheets (Parentheticals)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ConsolidatedIncomeStatement" id="oprx_r_ConsolidatedIncomeStatement">
        <link:definition>995303 - Statement - Consolidated Statements of Operations</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ShareholdersEquityType2or3" id="oprx_r_ShareholdersEquityType2or3">
        <link:definition>995304 - Statement - Consolidated Statement of Stockholders&#8217; Equity</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ConsolidatedCashFlow" id="oprx_r_ConsolidatedCashFlow">
        <link:definition>995305 - Statement - Consolidated Statements of Cash Flows</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/OrganizationandNatureofBusiness" id="oprx_r_OrganizationandNatureofBusiness">
        <link:definition>995306 - Disclosure - Organization and Nature of Business</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/SummaryofSignificantAccountingPolicies" id="oprx_r_SummaryofSignificantAccountingPolicies">
        <link:definition>995307 - Disclosure - Summary of Significant Accounting Policies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/Acquisitions" id="oprx_r_Acquisitions">
        <link:definition>995308 - Disclosure - Acquisitions</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/InvestmentSecurities" id="oprx_r_InvestmentSecurities">
        <link:definition>995309 - Disclosure - Investment Securities</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/PrepaidExpenses" id="oprx_r_PrepaidExpenses">
        <link:definition>995310 - Disclosure - Prepaid Expenses</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/PropertyandEquipment" id="oprx_r_PropertyandEquipment">
        <link:definition>995311 - Disclosure - Property and Equipment</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/GoodwillandIntangibleAssets" id="oprx_r_GoodwillandIntangibleAssets">
        <link:definition>995312 - Disclosure - Goodwill and Intangible Assets</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/DeferredRevenue" id="oprx_r_DeferredRevenue">
        <link:definition>995313 - Disclosure - Deferred Revenue</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/RelatedPartyTransactions" id="oprx_r_RelatedPartyTransactions">
        <link:definition>995314 - Disclosure - Related Party Transactions</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/StockholdersEquity" id="oprx_r_StockholdersEquity">
        <link:definition>995315 - Disclosure - Stockholders' Equity</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/StockBasedCompensation" id="oprx_r_StockBasedCompensation">
        <link:definition>995316 - Disclosure - Stock Based Compensation</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/LongTermDebt" id="oprx_r_LongTermDebt">
        <link:definition>995317 - Disclosure - Long-Term Debt</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/Leases" id="oprx_r_Leases">
        <link:definition>995318 - Disclosure - Leases</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/MajorCustomersandVendors" id="oprx_r_MajorCustomersandVendors">
        <link:definition>995319 - Disclosure - Major Customers and Vendors</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/IncomeTaxes" id="oprx_r_IncomeTaxes">
        <link:definition>995320 - Disclosure - Income Taxes</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/CommitmentsandContingentLiabilities" id="oprx_r_CommitmentsandContingentLiabilities">
        <link:definition>995321 - Disclosure - Commitments and Contingent Liabilities</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/RetirementPlan" id="oprx_r_RetirementPlan">
        <link:definition>995322 - Disclosure - Retirement Plan</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/SubsequentEvents" id="oprx_r_SubsequentEvents">
        <link:definition>995323 - Disclosure - Subsequent Events</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/AccountingPoliciesByPolicy" id="oprx_r_AccountingPoliciesByPolicy">
        <link:definition>996000 - Disclosure - Accounting Policies, by Policy (Policies)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/SummaryofSignificantAccountingPoliciesTables" id="oprx_r_SummaryofSignificantAccountingPoliciesTables">
        <link:definition>996001 - Disclosure - Summary of Significant Accounting Policies (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/AcquisitionsTables" id="oprx_r_AcquisitionsTables">
        <link:definition>996002 - Disclosure - Acquisitions (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/PrepaidExpensesTables" id="oprx_r_PrepaidExpensesTables">
        <link:definition>996003 - Disclosure - Prepaid Expenses (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/PropertyandEquipmentTables" id="oprx_r_PropertyandEquipmentTables">
        <link:definition>996004 - Disclosure - Property and Equipment (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/GoodwillandIntangibleAssetsTables" id="oprx_r_GoodwillandIntangibleAssetsTables">
        <link:definition>996005 - Disclosure - Goodwill and Intangible Assets (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/DeferredRevenueTables" id="oprx_r_DeferredRevenueTables">
        <link:definition>996006 - Disclosure - Deferred Revenue (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/StockBasedCompensationTables" id="oprx_r_StockBasedCompensationTables">
        <link:definition>996007 - Disclosure - Stock Based Compensation (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/LongTermDebtTables" id="oprx_r_LongTermDebtTables">
        <link:definition>996008 - Disclosure - Long-Term Debt (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/LeasesTables" id="oprx_r_LeasesTables">
        <link:definition>996009 - Disclosure - Leases (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/MajorCustomersandVendorsTables" id="oprx_r_MajorCustomersandVendorsTables">
        <link:definition>996010 - Disclosure - Major Customers and Vendors (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/IncomeTaxesTables" id="oprx_r_IncomeTaxesTables">
        <link:definition>996011 - Disclosure - Income Taxes (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/SummaryofSignificantAccountingPoliciesDetails" id="oprx_r_SummaryofSignificantAccountingPoliciesDetails">
        <link:definition>996012 - Disclosure - Summary of Significant Accounting Policies (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofChangesintheAllowanceforCreditLossesTable" id="oprx_r_ScheduleofChangesintheAllowanceforCreditLossesTable">
        <link:definition>996013 - Disclosure - Summary of Significant Accounting Policies (Details) - Schedule of Changes in the Allowance for Credit Losses</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofRevenueisEarnedfromLifeSciencesCompaniesTable" id="oprx_r_ScheduleofRevenueisEarnedfromLifeSciencesCompaniesTable">
        <link:definition>996014 - Disclosure - Summary of Significant Accounting Policies (Details) - Schedule of Revenue is Earned from Life Sciences Companies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofPayAnyDividendsintheFutureTable" id="oprx_r_ScheduleofPayAnyDividendsintheFutureTable">
        <link:definition>996015 - Disclosure - Summary of Significant Accounting Policies (Details) - Schedule of Pay Any Dividends in the Future</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofWeightedAverageSharesOutstandingandtheBasicandDilutedEarningsPerCommonShareTable" id="oprx_r_ScheduleofWeightedAverageSharesOutstandingandtheBasicandDilutedEarningsPerCommonShareTable">
        <link:definition>996016 - Disclosure - Summary of Significant Accounting Policies (Details) - Schedule of Weighted Average Shares Outstanding and the Basic and Diluted Earnings Per Common Share</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/AcquisitionsDetails" id="oprx_r_AcquisitionsDetails">
        <link:definition>996017 - Disclosure - Acquisitions (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofAcquisitionDateFairValueofConsiderationTransferredTable" id="oprx_r_ScheduleofAcquisitionDateFairValueofConsiderationTransferredTable">
        <link:definition>996018 - Disclosure - Acquisitions (Details) - Schedule of Acquisition Date Fair Value of Consideration Transferred</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofEstimatedFairValueofAssetsAcquiredandLiabilitiesTable" id="oprx_r_ScheduleofEstimatedFairValueofAssetsAcquiredandLiabilitiesTable">
        <link:definition>996019 - Disclosure - Acquisitions (Details) - Schedule of Estimated Fair Value of Assets Acquired and Liabilities</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofIdentifiableIntangiblesareBeingAmortizedonaStraightLineBasisTable" id="oprx_r_ScheduleofIdentifiableIntangiblesareBeingAmortizedonaStraightLineBasisTable">
        <link:definition>996020 - Disclosure - Acquisitions (Details) - Schedule of Identifiable Intangibles are Being Amortized on a Straight Line Basis</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofRevenueandNetIncomeofMedicxHealthIncludedintheCompanysConsolidatedStatementofOperationsTable" id="oprx_r_ScheduleofRevenueandNetIncomeofMedicxHealthIncludedintheCompanysConsolidatedStatementofOperationsTable">
        <link:definition>996021 - Disclosure - Acquisitions (Details) - Schedule of Revenue and Net Income of Medicx Health Included in the Company&#8217;s Consolidated Statement of Operations</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofProFormaConsolidatedStatementofOperationsTable" id="oprx_r_ScheduleofProFormaConsolidatedStatementofOperationsTable">
        <link:definition>996022 - Disclosure - Acquisitions (Details) - Schedule of Pro-Forma Consolidated Statement of Operations</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/InvestmentSecuritiesDetails" id="oprx_r_InvestmentSecuritiesDetails">
        <link:definition>996023 - Disclosure - Investment Securities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofPrepaidExpensesTable" id="oprx_r_ScheduleofPrepaidExpensesTable">
        <link:definition>996024 - Disclosure - Prepaid Expenses (Details) - Schedule of Prepaid Expenses</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/PropertyandEquipmentDetails" id="oprx_r_PropertyandEquipmentDetails">
        <link:definition>996025 - Disclosure - Property and Equipment (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofOwnedEquipmentRecordedatCostTable" id="oprx_r_ScheduleofOwnedEquipmentRecordedatCostTable">
        <link:definition>996026 - Disclosure - Property and Equipment (Details) - Schedule of Owned Equipment Recorded at Cost</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/GoodwillandIntangibleAssetsDetails" id="oprx_r_GoodwillandIntangibleAssetsDetails">
        <link:definition>996027 - Disclosure - Goodwill and Intangible Assets (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofGoodwillontheConsolidatedBalanceSheetTable" id="oprx_r_ScheduleofGoodwillontheConsolidatedBalanceSheetTable">
        <link:definition>996028 - Disclosure - Goodwill and Intangible Assets (Details) - Schedule of Goodwill on the Consolidated Balance Sheet</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofIntangibleAssetsIncludedontheConsolidatedBalanceSheetsTable" id="oprx_r_ScheduleofIntangibleAssetsIncludedontheConsolidatedBalanceSheetsTable">
        <link:definition>996029 - Disclosure - Goodwill and Intangible Assets (Details) - Schedule of Intangible Assets Included on the Consolidated Balance Sheets</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofIntangiblesareBeingAmortizedonaStraightLineBasisTable" id="oprx_r_ScheduleofIntangiblesareBeingAmortizedonaStraightLineBasisTable">
        <link:definition>996030 - Disclosure - Goodwill and Intangible Assets (Details) - Schedule of Intangibles are Being Amortized on a Straight-Line Basis</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
<!-- [WMV5][XcpuxYn59dz7vgYynUDuwG7r97K2jUTysl7vcz0lJt/tSeJz73kx1cLt0ZFF2SK/vxBCY0vdSrY3zgwHHioNV2cohiuDFf+hwvm7ENIq/CcPNpwjKdmt1EcmBHkr6foMwUdCMU0KgYNE/mZNJuW3ryd82RIH0pP1kUe6yHBLGmLGnzkwDycshQOPbrmyOeQRZNv4chOO0HeSIf4P7BPwUh8+kCGx+nMUoC4jY/8JlmOXgLpC1qwQ0M+4zEmelyiBY1Y2wSe9B4Q=] CSR-->
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofFutureAmortizationExpensesofIntangiblesAssetsTable" id="oprx_r_ScheduleofFutureAmortizationExpensesofIntangiblesAssetsTable">
        <link:definition>996031 - Disclosure - Goodwill and Intangible Assets (Details) - Schedule of Future Amortization Expenses of Intangibles Assets</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/DeferredRevenueDetails" id="oprx_r_DeferredRevenueDetails">
        <link:definition>996032 - Disclosure - Deferred Revenue (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofDeferredRevenueTable" id="oprx_r_ScheduleofDeferredRevenueTable">
        <link:definition>996033 - Disclosure - Deferred Revenue (Details) - Schedule of Deferred Revenue</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/RelatedPartyTransactionsDetails" id="oprx_r_RelatedPartyTransactionsDetails">
        <link:definition>996034 - Disclosure - Related Party Transactions (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/StockholdersEquityDetails" id="oprx_r_StockholdersEquityDetails">
        <link:definition>996035 - Disclosure - Stockholders' Equity (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/StockBasedCompensationDetails" id="oprx_r_StockBasedCompensationDetails">
        <link:definition>996036 - Disclosure - Stock Based Compensation (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofOptionActivityTable" id="oprx_r_ScheduleofOptionActivityTable">
        <link:definition>996037 - Disclosure - Stock Based Compensation (Details) - Schedule of Option Activity</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofTotalOptionsOutstandingTable" id="oprx_r_ScheduleofTotalOptionsOutstandingTable">
        <link:definition>996038 - Disclosure - Stock Based Compensation (Details) - Schedule of Total Options Outstanding</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofCompanysNonVestedOptionsTable" id="oprx_r_ScheduleofCompanysNonVestedOptionsTable">
        <link:definition>996039 - Disclosure - Stock Based Compensation (Details) - Schedule of Company&#8217;s Non-Vested Options</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofRestrictedStockUnitTable" id="oprx_r_ScheduleofRestrictedStockUnitTable">
        <link:definition>996040 - Disclosure - Stock Based Compensation (Details) - Schedule of Restricted Stock Unit</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/LongTermDebtDetails" id="oprx_r_LongTermDebtDetails">
        <link:definition>996041 - Disclosure - Long-Term Debt (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofLongTermDebtTable" id="oprx_r_ScheduleofLongTermDebtTable">
        <link:definition>996042 - Disclosure - Long-Term Debt (Details) - Schedule of Long Term Debt</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofMaximumLeverageRatioTable" id="oprx_r_ScheduleofMaximumLeverageRatioTable">
        <link:definition>996043 - Disclosure - Long-Term Debt (Details) - Schedule of Maximum Leverage Ratio</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofPaymentsDueontheLoanTable" id="oprx_r_ScheduleofPaymentsDueontheLoanTable">
        <link:definition>996044 - Disclosure - Long-Term Debt (Details) - Schedule of Payments Due on the Loan</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/LeasesDetails" id="oprx_r_LeasesDetails">
        <link:definition>996045 - Disclosure - Leases (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofLeaseCostTable" id="oprx_r_ScheduleofLeaseCostTable">
        <link:definition>996046 - Disclosure - Leases (Details) - Schedule of Lease Cost</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofFutureMinimumLeasePaymentsTable" id="oprx_r_ScheduleofFutureMinimumLeasePaymentsTable">
        <link:definition>996047 - Disclosure - Leases (Details) - Schedule of Future Minimum Lease Payments</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/MajorCustomersandVendorsDetails" id="oprx_r_MajorCustomersandVendorsDetails">
        <link:definition>996048 - Disclosure - Major Customers and Vendors (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofCustomersAccountedPercentageofRevenueTable" id="oprx_r_ScheduleofCustomersAccountedPercentageofRevenueTable">
        <link:definition>996049 - Disclosure - Major Customers and Vendors (Details) - Schedule of Customers Accounted Percentage of Revenue</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/IncomeTaxesDetails" id="oprx_r_IncomeTaxesDetails">
        <link:definition>996050 - Disclosure - Income Taxes (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofFederalIncomeTaxTable" id="oprx_r_ScheduleofFederalIncomeTaxTable">
        <link:definition>996051 - Disclosure - Income Taxes (Details) - Schedule of Federal Income Tax</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/ScheduleofNetDeferredTaxTable" id="oprx_r_ScheduleofNetDeferredTaxTable">
        <link:definition>996052 - Disclosure - Income Taxes (Details) - Schedule of Net Deferred Tax</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/CommitmentsandContingentLiabilitiesDetails" id="oprx_r_CommitmentsandContingentLiabilitiesDetails">
        <link:definition>996053 - Disclosure - Commitments and Contingent Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/RetirementPlanDetails" id="oprx_r_RetirementPlanDetails">
        <link:definition>996054 - Disclosure - Retirement Plan (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.optimizerx.com/role/DocumentAndEntityInformation" id="DocumentAndEntityInformation">
        <link:definition>000 - Document - Document And Entity Information</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
      </link:roleType>
    </xs:appinfo>
  </xs:annotation>
  <xs:import namespace="http://www.xbrl.org/2003/instance" schemaLocation="http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/2003/linkbase" schemaLocation="http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd"/>
  <xs:import namespace="http://fasb.org/us-types/2023" schemaLocation="https://xbrl.fasb.org/us-gaap/2023/elts/us-types-2023.xsd"/>
  <xs:import namespace="http://www.xbrl.org/dtr/type/2022-03-31" schemaLocation="https://www.xbrl.org/dtr/type/2022-03-31/types.xsd"/>
  <xs:import namespace="http://xbrl.org/2005/xbrldt" schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd"/>
  <xs:import namespace="http://fasb.org/srt-types/2023" schemaLocation="https://xbrl.fasb.org/srt/2023/elts/srt-types-2023.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/sic/2023" schemaLocation="https://xbrl.sec.gov/sic/2023/sic-2023.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/ecd-sub/2023" schemaLocation="https://xbrl.sec.gov/ecd/2023/ecd-sub-2023.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/dei-sub/2023" schemaLocation="https://xbrl.sec.gov/dei/2023/dei-sub-2023.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/ecd/2023" schemaLocation="https://xbrl.sec.gov/ecd/2023/ecd-2023.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/ecd-sub/2023" schemaLocation="https://xbrl.sec.gov/ecd/2023/ecd-sub-2023.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/dei-sub/2023" schemaLocation="https://xbrl.sec.gov/dei/2023/dei-sub-2023.xsd"/>
  <xs:element name="MrWilliamJFebboMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_MrWilliamJFebboMember"/>
  <xs:element name="MsMarionOdenceFordMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_MsMarionOdenceFordMember"/>
  <xs:element name="ScheduleOfChangesInTheAllowanceForCreditLossesAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfChangesInTheAllowanceForCreditLossesAbstract"/>
  <xs:element name="ScheduleOfRevenueIsEarnedFromLifeSciencesCompaniesAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfRevenueIsEarnedFromLifeSciencesCompaniesAbstract"/>
  <xs:element name="ScheduleOfPayAnyDividendsInTheFutureAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfPayAnyDividendsInTheFutureAbstract"/>
  <xs:element name="ScheduleOfWeightedAverageSharesOutstandingAndTheBasicAndDilutedEarningsPerCommonShareAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfWeightedAverageSharesOutstandingAndTheBasicAndDilutedEarningsPerCommonShareAbstract"/>
  <xs:element name="ScheduleOfEstimatedFairValueOfAssetsAcquiredAndLiabilitiesAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfEstimatedFairValueOfAssetsAcquiredAndLiabilitiesAbstract"/>
  <xs:element name="ScheduleOfIdentifiableIntangiblesAreBeingAmortizedOnAStraightLineBasisAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfIdentifiableIntangiblesAreBeingAmortizedOnAStraightLineBasisAbstract"/>
  <xs:element name="PrepaidExpensesAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_PrepaidExpensesAbstract"/>
  <xs:element name="ScheduleOfPrepaidExpensesAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfPrepaidExpensesAbstract"/>
  <xs:element name="ScheduleOfOwnedEquipmentRecordedAtCostAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfOwnedEquipmentRecordedAtCostAbstract"/>
  <xs:element name="ScheduleOfGoodwillOnTheConsolidatedBalanceSheetAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfGoodwillOnTheConsolidatedBalanceSheetAbstract"/>
  <xs:element name="ScheduleOfIntangibleAssetsIncludedOnTheConsolidatedBalanceSheetsAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfIntangibleAssetsIncludedOnTheConsolidatedBalanceSheetsAbstract"/>
  <xs:element name="ScheduleOfIntangiblesAreBeingAmortizedOnAStraightLineBasisAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfIntangiblesAreBeingAmortizedOnAStraightLineBasisAbstract"/>
  <xs:element name="ScheduleOfFutureAmortizationExpensesOfIntangiblesAssetsAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfFutureAmortizationExpensesOfIntangiblesAssetsAbstract"/>
  <xs:element name="ScheduleOfDeferredRevenueAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfDeferredRevenueAbstract"/>
  <xs:element name="ScheduleOfOptionActivityAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfOptionActivityAbstract"/>
  <xs:element name="ScheduleOfTotalOptionsOutstandingAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfTotalOptionsOutstandingAbstract"/>
  <xs:element name="ScheduleOfCompanySNonVestedOptionsAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfCompanySNonVestedOptionsAbstract"/>
  <xs:element name="ScheduleOfRestrictedStockUnitAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfRestrictedStockUnitAbstract"/>
  <xs:element name="ScheduleOfLongTermDebtAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfLongTermDebtAbstract"/>
  <xs:element name="ScheduleOfMaximumLeverageRatioAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfMaximumLeverageRatioAbstract"/>
  <xs:element name="ScheduleOfPaymentsDueOnTheLoanAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfPaymentsDueOnTheLoanAbstract"/>
  <xs:element name="ScheduleOfLeaseCostAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfLeaseCostAbstract"/>
  <xs:element name="ScheduleOfFutureMinimumLeasePaymentsAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfFutureMinimumLeasePaymentsAbstract"/>
  <xs:element name="ScheduleOfCustomersAccountedPercentageOfRevenueAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfCustomersAccountedPercentageOfRevenueAbstract"/>
  <xs:element name="ScheduleOfFederalIncomeTaxAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfFederalIncomeTaxAbstract"/>
  <xs:element name="ScheduleOfNetDeferredTaxAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfNetDeferredTaxAbstract"/>
  <xs:element name="UnlabeledAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_UnlabeledAbstract"/>
  <xs:element name="NonCurrentLiabilitiesAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_NonCurrentLiabilitiesAbstract"/>
  <xs:element name="UnlabeledAbstract0" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_UnlabeledAbstract0"/>
  <xs:element name="StockBasedCompensationExpenseAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_StockBasedCompensationExpenseAbstract"/>
  <xs:element name="IssuanceOfCommonStockAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_IssuanceOfCommonStockAbstract"/>
  <xs:element name="StockBasedCompensationExpenseAbstract0" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_StockBasedCompensationExpenseAbstract0"/>
  <xs:element name="IssuanceOfCommonStockAbstract0" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_IssuanceOfCommonStockAbstract0"/>
  <xs:element name="UnlabeledAbstract1" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_UnlabeledAbstract1"/>
  <xs:element name="UnlabeledAbstract2" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_UnlabeledAbstract2"/>
  <xs:element name="UnlabeledAbstract3" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_UnlabeledAbstract3"/>
  <xs:element name="OtherIntangibleAssetsAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_OtherIntangibleAssetsAbstract"/>
  <xs:element name="OtherIntangibleAssetsAbstract0" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_OtherIntangibleAssetsAbstract0"/>
  <xs:element name="FederalIncomeTaxBenefitExpenseAttributableToAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_FederalIncomeTaxBenefitExpenseAttributableToAbstract"/>
  <xs:element name="DeferredTaxAssetsAttributableToAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_DeferredTaxAssetsAttributableToAbstract"/>
  <xs:element name="UnlabeledAbstract4" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_UnlabeledAbstract4"/>
  <xs:element name="DeferredTaxLiabilitiesAttributableToAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_DeferredTaxLiabilitiesAttributableToAbstract"/>
  <xs:element name="PatentRightsNetNonCurrent" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_PatentRightsNetNonCurrent"/>
  <xs:element name="TechnologyAssetsNet" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_TechnologyAssetsNet"/>
  <xs:element name="RevenueSharePayableCurrent" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_RevenueSharePayableCurrent"/>
  <xs:element name="TreasuryStockParValue" type="dtr:perShareItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="oprx_TreasuryStockParValue"/>
  <xs:element name="TreasuryStockSharesPurchased" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="oprx_TreasuryStockSharesPurchased"/>
  <xs:element name="IncreaseDecreaseInRevenueSharePayable" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_IncreaseDecreaseInRevenueSharePayable"/>
  <xs:element name="ProceedsFromExerciseOfStockOptionsNetOfCashPaidForWithholdingTaxes" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_ProceedsFromExerciseOfStockOptionsNetOfCashPaidForWithholdingTaxes"/>
  <xs:element name="ReductionOfEvinceMedPurchasePriceForAmountsPreviouslyPaid" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_ReductionOfEvinceMedPurchasePriceForAmountsPreviouslyPaid"/>
  <xs:element name="SharesIssuedInConnectionWithAcquisitions" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_SharesIssuedInConnectionWithAcquisitions"/>
  <xs:element name="SummaryofSignificantAccountingPoliciesTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_SummaryofSignificantAccountingPoliciesTable"/>
  <xs:element name="SummaryofSignificantAccountingPoliciesLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SummaryofSignificantAccountingPoliciesLineItems"/>
  <xs:element name="PrepaidExpensesTextBlock" type="dtr:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_PrepaidExpensesTextBlock"/>
  <xs:element name="DisaggregationOfRevenuePolicyTextBlock" type="dtr:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_DisaggregationOfRevenuePolicyTextBlock"/>
  <xs:element name="RevenueRecognitionAndRevenueShareExpensePolicyTextBlock" type="dtr:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_RevenueRecognitionAndRevenueShareExpensePolicyTextBlock"/>
  <xs:element name="NotYetAdoptedPolicyPolicyTextBlock" type="dtr:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_NotYetAdoptedPolicyPolicyTextBlock"/>
  <xs:element name="ProFormaConsolidatedStatementOfOperationsTableTextBlock" type="dtr:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ProFormaConsolidatedStatementOfOperationsTableTextBlock"/>
  <xs:element name="ScheduleOfPrepaidExpensesTableTextBlock" type="dtr:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfPrepaidExpensesTableTextBlock"/>
  <xs:element name="ScheduleOfMaximumLeverageRatioTableTextBlock" type="dtr:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfMaximumLeverageRatioTableTextBlock"/>
  <xs:element name="RevenueRecognizedTime" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_RevenueRecognizedTime"/>
  <xs:element name="SummaryofSignificantAccountingPoliciesDetailsScheduleofPayAnyDividendsintheFutureTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_SummaryofSignificantAccountingPoliciesDetailsScheduleofPayAnyDividendsintheFutureTable"/>
  <xs:element name="SummaryofSignificantAccountingPoliciesDetailsScheduleofPayAnyDividendsintheFutureLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SummaryofSignificantAccountingPoliciesDetailsScheduleofPayAnyDividendsintheFutureLineItems"/>
  <xs:element name="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsTurnoverforfeitureRate" type="dtr:percentItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsTurnoverforfeitureRate"/>
  <xs:element name="WeightedAverageGrantDateFairValueinDollarsPerShare" type="dtr:perShareItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_WeightedAverageGrantDateFairValueinDollarsPerShare"/>
  <xs:element name="EffectOfDilutiveSecuritiesShares" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_EffectOfDilutiveSecuritiesShares"/>
  <xs:element name="EffectOfDilutiveSecuritiesPerShareAmount" type="dtr:perShareItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_EffectOfDilutiveSecuritiesPerShareAmount"/>
  <xs:element name="BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentTaxesReceivable" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentTaxesReceivable"/>
  <xs:element name="BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedTrademarkAndPatentIntangible" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedTrademarkAndPatentIntangible"/>
  <xs:element name="BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedTechnologyIntangibles" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedTechnologyIntangibles"/>
  <xs:element name="BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOperatingLeaseRightofuseAssets" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOperatingLeaseRightofuseAssets"/>
  <xs:element name="BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeposits" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeposits"/>
  <xs:element name="BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilitiesAccruedExpenses" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilitiesAccruedExpenses"/>
  <xs:element name="RevenueShareAndExclusivityPayments" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_RevenueShareAndExclusivityPayments"/>
  <xs:element name="PropertyPlantandEquipmentData" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_PropertyPlantandEquipmentData"/>
  <xs:element name="AcquisitionsOnGoodwill" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_AcquisitionsOnGoodwill"/>
  <xs:element name="GoodwillandIntangibleAssetsDetailsScheduleofIntangiblesareBeingAmortizedonaStraightLineBasisTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_GoodwillandIntangibleAssetsDetailsScheduleofIntangiblesareBeingAmortizedonaStraightLineBasisTable"/>
  <xs:element name="GoodwillandIntangibleAssetsDetailsScheduleofIntangiblesareBeingAmortizedonaStraightLineBasisLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_GoodwillandIntangibleAssetsDetailsScheduleofIntangiblesareBeingAmortizedonaStraightLineBasisLineItems"/>
  <xs:element name="WeightedAverageExercisePriceExercised" type="dtr:perShareItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_WeightedAverageExercisePriceExercised"/>
  <xs:element name="ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisableInPeriodWeightedAverageExercisePrice" type="dtr:perShareItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisableInPeriodWeightedAverageExercisePrice"/>
  <xs:element name="SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsSharesOutstandingBeginning" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="oprx_SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsSharesOutstandingBeginning"/>
  <xs:element name="ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsSharesIssued" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsSharesIssued"/>
  <xs:element name="WeightedgrantdatefairvalueSharesissued" type="dtr:perShareItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_WeightedgrantdatefairvalueSharesissued"/>
  <xs:element name="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageGrantDateFairValueWithheldAndCancelled" type="dtr:perShareItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageGrantDateFairValueWithheldAndCancelled"/>
  <xs:element name="SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsSharesVestedAndIssued" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsSharesVestedAndIssued"/>
  <xs:element name="SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsWeightedAverageGrantDateFairValueVestedAndIssued" type="dtr:perShareItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsWeightedAverageGrantDateFairValueVestedAndIssued"/>
  <xs:element name="LongTermDebtDetailsScheduleofMaximumLeverageRatioTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_LongTermDebtDetailsScheduleofMaximumLeverageRatioTable"/>
  <xs:element name="LongTermDebtDetailsScheduleofMaximumLeverageRatioLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_LongTermDebtDetailsScheduleofMaximumLeverageRatioLineItems"/>
  <xs:element name="LeverageRatio" type="xbrli:pureItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_LeverageRatio"/>
  <xs:element name="LongTermDebtDetailsScheduleofPaymentsDueontheLoanTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_LongTermDebtDetailsScheduleofPaymentsDueontheLoanTable"/>
  <xs:element name="LongTermDebtDetailsScheduleofPaymentsDueontheLoanLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_LongTermDebtDetailsScheduleofPaymentsDueontheLoanLineItems"/>
  <xs:element name="TotalLeaseLiabilities" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_TotalLeaseLiabilities"/>
  <xs:element name="FederalIncomeTaxStateTaxEffectNetOfFederalBenefit" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_FederalIncomeTaxStateTaxEffectNetOfFederalBenefit"/>
  <xs:element name="FederalIncomeTaxOptionExerciseBenefitsNetOfSection162MLimitations" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_FederalIncomeTaxOptionExerciseBenefitsNetOfSection162MLimitations"/>
  <xs:element name="FederalIncomeTaxOtherAdjustments" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_FederalIncomeTaxOtherAdjustments"/>
  <xs:element name="FederalIncomeTaxExpensesBenefitValueAllowance" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_FederalIncomeTaxExpensesBenefitValueAllowance"/>
  <xs:element name="DeferredTaxAssetsOperatingLeaseLiability" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_DeferredTaxAssetsOperatingLeaseLiability"/>
  <xs:element name="DeferredTaxLiabilitiesOperatingLeaseRightOfUseAssets" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_DeferredTaxLiabilitiesOperatingLeaseRightOfUseAssets"/>
  <xs:element name="NetDeferredTaxliabilityAssets" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_NetDeferredTaxliabilityAssets"/>
  <xs:element name="SummaryofSignificantAccountingPoliciesDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_SummaryofSignificantAccountingPoliciesDetailsTable"/>
  <xs:element name="SummaryofSignificantAccountingPoliciesDetailsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SummaryofSignificantAccountingPoliciesDetailsLineItems"/>
  <xs:element name="AcquisitionsDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_AcquisitionsDetailsTable"/>
  <xs:element name="IssuanceOfSharesOfCommonStock" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="oprx_IssuanceOfSharesOfCommonStock"/>
  <xs:element name="BusinessAcquisitionCommonStockValue" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_BusinessAcquisitionCommonStockValue"/>
  <xs:element name="PurchasePrice" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_PurchasePrice"/>
  <xs:element name="GoodwillDeductibleTaxLife" type="xbrli:durationItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_GoodwillDeductibleTaxLife"/>
  <xs:element name="TransactionDue" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_TransactionDue"/>
  <xs:element name="AccessProducts" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_AccessProducts"/>
  <xs:element name="RevenueFromContract" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_RevenueFromContract"/>
  <xs:element name="StockholdersEquityDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_StockholdersEquityDetailsTable"/>
  <xs:element name="StockholdersEquityDetailsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_StockholdersEquityDetailsLineItems"/>
  <xs:element name="GrossProceedsOfCommonStockAmount" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_GrossProceedsOfCommonStockAmount"/>
  <xs:element name="CommonStockValued" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_CommonStockValued"/>
  <xs:element name="RepurchaseOfCommonStockinShares" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_RepurchaseOfCommonStockinShares"/>
  <xs:element name="StockBasedCompensationDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_StockBasedCompensationDetailsTable"/>
  <xs:element name="StockBasedCompensationDetailsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_StockBasedCompensationDetailsLineItems"/>
  <xs:element name="SharesOfCommonStockOptions" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SharesOfCommonStockOptions"/>
  <xs:element name="CommonStockRestrictedStockUnit" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CommonStockRestrictedStockUnit"/>
  <xs:element name="FairMarketValueRate" type="dtr:percentItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_FairMarketValueRate"/>
  <xs:element name="SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm2" type="xbrli:durationItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm2"/>
  <xs:element name="GrantedRestrictedStockDescription" type="xbrli:stringItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_GrantedRestrictedStockDescription"/>
  <xs:element name="RestrictedStockGrantedRemainsValue" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_RestrictedStockGrantedRemainsValue"/>
  <xs:element name="RemainsToBeRecognizedOverAPeriod" type="xbrli:durationItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_RemainsToBeRecognizedOverAPeriod"/>
  <xs:element name="OptionsExercisedValue" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_OptionsExercisedValue"/>
  <xs:element name="RestrictedStockUnits" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="oprx_RestrictedStockUnits"/>
  <xs:element name="StockIssuedDuringPeriodSharesRestrictedStocksAwardGross" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_StockIssuedDuringPeriodSharesRestrictedStocksAwardGross"/>
  <xs:element name="GrantDateFairValueOver" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_GrantDateFairValueOver"/>
  <xs:element name="MarketBasedRestrictedStockUnits" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="oprx_MarketBasedRestrictedStockUnits"/>
  <xs:element name="LongTermDebtDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_LongTermDebtDetailsTable"/>
  <xs:element name="LongTermDebtDetailsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_LongTermDebtDetailsLineItems"/>
  <xs:element name="TermLoanPercentage" type="dtr:percentItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_TermLoanPercentage"/>
  <xs:element name="LeverageDescription" type="xbrli:stringItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_LeverageDescription"/>
  <xs:element name="MeasurementOfLeaseLiabilities" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_MeasurementOfLeaseLiabilities"/>
  <xs:element name="MajorCustomersandVendorsDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_MajorCustomersandVendorsDetailsTable"/>
  <xs:element name="MajorCustomersandVendorsDetailsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_MajorCustomersandVendorsDetailsLineItems"/>
  <xs:element name="FutureMinimumPayments" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_FutureMinimumPayments"/>
  <xs:element name="CustomerAMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CustomerAMember"/>
  <xs:element name="CustomerBMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CustomerBMember"/>
  <xs:element name="CustomerOneMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CustomerOneMember"/>
  <xs:element name="CustomerRelationshipIntangibleMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CustomerRelationshipIntangibleMember"/>
  <xs:element name="CustomerTwoMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CustomerTwoMember"/>
  <xs:element name="DecemberThirtyFirstTwentyTwentyFourMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_DecemberThirtyFirstTwentyTwentyFourMember"/>
  <xs:element name="EntityOneMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_EntityOneMember"/>
  <xs:element name="EntityTwoMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_EntityTwoMember"/>
  <xs:element name="EvinceMedMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_EvinceMedMember"/>
  <xs:element name="ExercisePriceRangeFiveMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ExercisePriceRangeFiveMember"/>
  <xs:element name="ExercisePriceRangeFourMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ExercisePriceRangeFourMember"/>
  <xs:element name="ExercisePriceRangeMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ExercisePriceRangeMember"/>
  <xs:element name="ExercisePriceRangeOneMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ExercisePriceRangeOneMember"/>
  <xs:element name="ExercisePriceRangeThreeMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ExercisePriceRangeThreeMember"/>
  <xs:element name="ExercisePriceRangeTwoMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ExercisePriceRangeTwoMember"/>
  <xs:element name="FirstAnniversaryMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_FirstAnniversaryMember"/>
  <xs:element name="JuneThirtyTwentyTwentyFiveMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_JuneThirtyTwentyTwentyFiveMember"/>
  <xs:element name="JuneThreeZeroTwoZeroTwoFourMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_JuneThreeZeroTwoZeroTwoFourMember"/>
  <xs:element name="KeyPartnersMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_KeyPartnersMember"/>
  <xs:element name="MarchThirtyFirstTwentyTwentyFiveMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_MarchThirtyFirstTwentyTwentyFiveMember"/>
  <xs:element name="MarchThreeOneTwoZeroTwoFourMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_MarchThreeOneTwoZeroTwoFourMember"/>
  <xs:element name="MedicxHealthMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_MedicxHealthMember"/>
  <xs:element name="OneAgencyMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_OneAgencyMember"/>
  <xs:element name="PartnerAMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_PartnerAMember"/>
  <xs:element name="PartnerBMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_PartnerBMember"/>
  <xs:element name="PartnerCMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_PartnerCMember"/>
  <xs:element name="SecondAnniversaryMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SecondAnniversaryMember"/>
  <xs:element name="SeptemberThirtyTwentyTwentyFiveAndThereafterMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SeptemberThirtyTwentyTwentyFiveAndThereafterMember"/>
  <xs:element name="SeptemberThirtyTwentyTwentyFourMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SeptemberThirtyTwentyTwentyFourMember"/>
  <xs:element name="StockOptionsMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_StockOptionsMember"/>
  <xs:element name="TechnologyIntangiblesMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_TechnologyIntangiblesMember"/>
  <xs:element name="ThirdAnniversaryMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ThirdAnniversaryMember"/>
  <xs:element name="TotalIntanbleAssetsMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_TotalIntanbleAssetsMember"/>
  <xs:element name="TrademarkAndPatentIntangibleMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_TrademarkAndPatentIntangibleMember"/>
  <xs:element name="TwoEntitiesMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_TwoEntitiesMember"/>
  <xs:element name="TwoThousandTwentyOnePlanMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_TwoThousandTwentyOnePlanMember"/>
  <xs:element name="VestedOptionsOutstandingMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_VestedOptionsOutstandingMember"/>
  <xs:element name="RetirementPlanAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_RetirementPlanAbstract"/>
  <xs:element name="ScheduleOfIdentifiableIntangiblesAreBeingAmortizedOnAStraightLineBasisLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfIdentifiableIntangiblesAreBeingAmortizedOnAStraightLineBasisLineItems"/>
  <xs:element name="ScheduleOfRevenueAndNetIncomeOfMedicxHealthIncludedInTheCompanysConsolidatedStatementOfOperationsAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfRevenueAndNetIncomeOfMedicxHealthIncludedInTheCompanysConsolidatedStatementOfOperationsAbstract"/>
  <xs:element name="DocumentAndEntityInformationAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_DocumentAndEntityInformationAbstract"/>
</xs:schema>
