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<link:definition>002 - Statement - Consolidated Balance Sheets</link:definition>
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<link:definition>003 - Statement - Consolidated Balance Sheets (Parenthetical)</link:definition>
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<link:definition>004 - Statement - Consolidated Statements of Operations</link:definition>
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<link:definition>005 - Statement - Consolidated Statement of Stockholders' Equity</link:definition>
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<link:definition>006 - Statement - Consolidated Statements of Cash Flows</link:definition>
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<link:definition>007 - Disclosure - Nature of Business</link:definition>
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<link:definition>008 - Disclosure - Summary of Significant Accounting Policies</link:definition>
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<link:definition>009 - Disclosure - Prepaid Expenses</link:definition>
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<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>010 - Disclosure - Property and Equipment</link:definition>
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<link:definition>011 - Disclosure - Web-Based Technology</link:definition>
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<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>012 - Disclosure - Patent and Trademarks</link:definition>
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<link:definition>013 - Disclosure - Deferred Revenue</link:definition>
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<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>014 - Disclosure - Related Party Transactions</link:definition>
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<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>015 - Disclosure - Preferred Stock</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>016 - Disclosure - Common Stock</link:definition>
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<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>017 - Disclosure - Stock Options</link:definition>
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<link:definition>018 - Disclosure - Warrants</link:definition>
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<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>019 - Disclosure - Operating Leases</link:definition>
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<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>020 - Disclosure - Major Customers</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
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<link:definition>021 - Disclosure - Income Taxes</link:definition>
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<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>022 - 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>
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<link:definition>023 - 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://OPRX/role/SubsequentEvents" id="SubsequentEvents">
<link:definition>024 - 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://OPRX/role/SummaryofSignificantAccountingPoliciesPolicies" id="SummaryofSignificantAccountingPoliciesPolicies">
<link:definition>025 - Disclosure - Summary of Significant Accounting Policies (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://OPRX/role/SummaryofSignificantAccountingPoliciesTables" id="SummaryofSignificantAccountingPoliciesTables">
<link:definition>026 - 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>
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<link:roleType roleURI="http://OPRX/role/PrepaidExpensesTables" id="PrepaidExpensesTables">
<link:definition>027 - Disclosure - Prepaid Expenses (Tables)</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:roleType roleURI="http://OPRX/role/PropertyandEquipmentTables" id="PropertyandEquipmentTables">
<link:definition>028 - 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://OPRX/role/WebBasedTechnologyTables" id="WebBasedTechnologyTables">
<link:definition>029 - Disclosure - Web-Based Technology (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://OPRX/role/PatentandTrademarksTables" id="PatentandTrademarksTables">
<link:definition>030 - Disclosure - Patent and Trademarks (Tables)</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:roleType roleURI="http://OPRX/role/StockOptionsTables" id="StockOptionsTables">
<link:definition>031 - Disclosure - Stock Options (Tables)</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:roleType roleURI="http://OPRX/role/WarrantsTables" id="WarrantsTables">
<link:definition>032 - Disclosure - Warrants (Tables)</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:roleType roleURI="http://OPRX/role/OperatingLeasesTables" id="OperatingLeasesTables">
<link:definition>033 - Disclosure - Operating Leases (Tables)</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:roleType roleURI="http://OPRX/role/MajorCustomersTables" id="MajorCustomersTables">
<link:definition>034 - Disclosure - Major Customers (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://OPRX/role/IncomeTaxesTables" id="IncomeTaxesTables">
<link:definition>035 - 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://OPRX/role/NatureOfBusinessDetails" id="NatureOfBusinessDetails">
<link:definition>036 - Disclosure - Nature of Business (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://OPRX/role/SummaryofSignificantAccountingPoliciesDetails" id="SummaryofSignificantAccountingPoliciesDetails">
<link:definition>037 - 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://OPRX/role/SummaryOfSignificantAccountingPoliciesDetailsTextual" id="SummaryOfSignificantAccountingPoliciesDetailsTextual">
<link:definition>038 - Disclosure - Summary of Significant Accounting Policies (Details Textual)</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://OPRX/role/PrepaidExpensesDetails" id="PrepaidExpensesDetails">
<link:definition>039 - Disclosure - Prepaid Expenses (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://OPRX/role/PropertyandEquipmentDetails" id="PropertyandEquipmentDetails">
<link:definition>040 - 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://OPRX/role/PropertyAndEquipmentDetailsTextual" id="PropertyAndEquipmentDetailsTextual">
<link:definition>041 - Disclosure - Property and Equipment (Details Textual)</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://OPRX/role/WebBasedTechnologyDetails" id="WebBasedTechnologyDetails">
<link:definition>042 - Disclosure - Web Based Technology (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://OPRX/role/WebBasedTechnologyDetailsTextual" id="WebBasedTechnologyDetailsTextual">
<link:definition>043 - Disclosure - Web-Based Technology (Details Textual)</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://OPRX/role/PatentandTrademarksDetails" id="PatentandTrademarksDetails">
<link:definition>044 - Disclosure - Patent and Trademarks (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://OPRX/role/PatentAndTrademarksDetailsTextual" id="PatentAndTrademarksDetailsTextual">
<link:definition>045 - Disclosure - Patent and Trademarks (Details Textual)</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://OPRX/role/DeferredRevenueDetails" id="DeferredRevenueDetails">
<link:definition>046 - 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://OPRX/role/RelatedPartyTransactionsDetails" id="RelatedPartyTransactionsDetails">
<link:definition>047 - 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>
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<link:roleType roleURI="http://OPRX/role/PreferredStockDetails" id="PreferredStockDetails">
<link:definition>048 - Disclosure - Preferred Stock (Details)</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:roleType roleURI="http://OPRX/role/CommonStockDetails" id="CommonStockDetails">
<link:definition>049 - Disclosure - Common Stock (Details)</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:roleType roleURI="http://OPRX/role/StockOptionsDetails" id="StockOptionsDetails">
<link:definition>050 - Disclosure - Stock Options (Details)</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:roleType roleURI="http://OPRX/role/StockOptionsDetailTextual" id="StockOptionsDetailTextual">
<link:definition>051 - Disclosure - Stock Options (Detail Textual)</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:roleType roleURI="http://OPRX/role/WarrantsDetails" id="WarrantsDetails">
<link:definition>052 - Disclosure - Warrants (Details)</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:roleType roleURI="http://OPRX/role/WarrantsDetails1" id="WarrantsDetails1">
<link:definition>053 - Disclosure - Warrants (Details 1)</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://OPRX/role/WarrantsDetailsTextual" id="WarrantsDetailsTextual">
<link:definition>054 - Disclosure - Warrants (Details Textual)</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://OPRX/role/OperatingLeasesDetails" id="OperatingLeasesDetails">
<link:definition>055 - Disclosure - Operating 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://OPRX/role/OperatingLeasesDetailsTextual" id="OperatingLeasesDetailsTextual">
<link:definition>056 - Disclosure - Operating Leases (Details Textual)</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://OPRX/role/MajorCustomersDetails" id="MajorCustomersDetails">
<link:definition>057 - Disclosure - Major Customers (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://OPRX/role/MajorCustomersDetailsTextual" id="MajorCustomersDetailsTextual">
<link:definition>058 - Disclosure - Major Customers (Details Textual)</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://OPRX/role/IncomeTaxesDetails" id="IncomeTaxesDetails">
<link:definition>059 - 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://OPRX/role/IncomeTaxesDetails1" id="IncomeTaxesDetails1">
<link:definition>060 - Disclosure - Income Taxes (Details 1)</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:roleType roleURI="http://OPRX/role/IncomeTaxesDetailsTextual" id="IncomeTaxesDetailsTextual">
<link:definition>061 - Disclosure - Income Taxes (Details Textual)</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://OPRX/role/CommitmentsAndContingentLiabilitiesDetails" id="CommitmentsAndContingentLiabilitiesDetails">
<link:definition>062 - 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>
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<link:roleType roleURI="http://OPRX/role/RetirementPlanDetails" id="RetirementPlanDetails">
<link:definition>063 - 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>
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<import namespace="http://www.xbrl.org/2003/instance" schemaLocation="http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd"/>
<import namespace="http://www.xbrl.org/2003/linkbase" schemaLocation="http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd"/>
<import namespace="http://xbrl.org/2005/xbrldt" schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd"/>
<import namespace="http://fasb.org/us-gaap/2016-01-31" schemaLocation="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd"/>
<import namespace="http://xbrl.sec.gov/invest/2013-01-31" schemaLocation="http://xbrl.sec.gov/invest/2013/invest-2013-01-31.xsd"/>
<import namespace="http://xbrl.sec.gov/country/2016-01-31" schemaLocation="http://xbrl.sec.gov/country/2016/country-2016-01-31.xsd"/>
<import namespace="http://xbrl.sec.gov/currency/2016-01-31" schemaLocation="http://xbrl.sec.gov/currency/2016/currency-2016-01-31.xsd"/>
<import namespace="http://xbrl.sec.gov/exch/2016-01-31" schemaLocation="http://xbrl.sec.gov/exch/2016/exch-2016-01-31.xsd"/>
<import namespace="http://xbrl.sec.gov/naics/2011-01-31" schemaLocation="http://xbrl.sec.gov/naics/2011/naics-2011-01-31.xsd"/>
<import namespace="http://xbrl.sec.gov/sic/2011-01-31" schemaLocation="http://xbrl.sec.gov/sic/2011/sic-2011-01-31.xsd"/>
<import namespace="http://xbrl.sec.gov/stpr/2011-01-31" schemaLocation="http://xbrl.sec.gov/stpr/2011/stpr-2011-01-31.xsd"/>
<import namespace="http://www.xbrl.org/2009/role/negated" schemaLocation="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd"/>
<import namespace="http://www.xbrl.org/2009/role/net" schemaLocation="http://www.xbrl.org/lrr/role/net-2009-12-16.xsd"/>
<import namespace="http://www.xbrl.org/2009/arcrole/fact-explanatoryFact" schemaLocation="http://www.xbrl.org/lrr/arcrole/factExplanatory-2009-12-16.xsd"/>
<import namespace="http://xbrl.sec.gov/dei/2014-01-31" schemaLocation="http://xbrl.sec.gov/dei/2014/dei-2014-01-31.xsd"/>
<import namespace="http://www.xbrl.org/dtr/type/numeric" schemaLocation="http://www.xbrl.org/dtr/type/numeric-2009-12-16.xsd"/>
<import namespace="http://www.xbrl.org/dtr/type/non-numeric" schemaLocation="http://www.xbrl.org/dtr/type/nonNumeric-2009-12-16.xsd"/>
<import namespace="http://fasb.org/us-types/2016-01-31" schemaLocation="http://xbrl.fasb.org/us-gaap/2016/elts/us-types-2016-01-31.xsd"/>
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<element name="RevenueSharePayableCurrent" id="oprx_RevenueSharePayableCurrent" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item"/>
<element name="StockPayable" id="oprx_StockPayable" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item"/>
<element name="RevenueShareExpense" id="oprx_RevenueShareExpense" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item"/>
<element name="StockPayableMember" id="oprx_StockPayableMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="StockIssuedDuringPeriodValueConsultants" id="oprx_StockIssuedDuringPeriodValueConsultants" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item"/>
<element name="StockIssuedDuringPeriodOfIssueStockRightsToOfficers" id="oprx_StockIssuedDuringPeriodOfIssueStockRightsToOfficers" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item"/>
<element name="StockIssuedDuringPeriodValueForLitigationSettlement" id="oprx_StockIssuedDuringPeriodValueForLitigationSettlement" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item"/>
<element name="StockIssuedDuringPeriodSharesForLitigationSettlement" id="oprx_StockIssuedDuringPeriodSharesForLitigationSettlement" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="StockIssuedDuringPeriodValueForStockPayable" id="oprx_StockIssuedDuringPeriodValueForStockPayable" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item"/>
<element name="StockIssuedDuringPeriodSharesForStockPayable" id="oprx_StockIssuedDuringPeriodSharesForStockPayable" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="StockOptionsIssuedForServices" id="oprx_StockOptionsIssuedForServices" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item"/>
<element name="IncreaseDecreaseInRevenueSharePayable" id="oprx_IncreaseDecreaseInRevenueSharePayable" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item"/>
<element name="PaymentsToAcquirePatientRights" id="oprx_PaymentsToAcquirePatientRights" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item"/>
<element name="PaymentsToAcquireWebsiteDevelopment" id="oprx_PaymentsToAcquireWebsiteDevelopment" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item"/>
<element name="PrepaidExpensesAbstract" id="oprx_PrepaidExpensesAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="PrepaidExpensesTextBlock" id="oprx_PrepaidExpensesTextBlock" type="nonnum:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="WebBasedTechnologyAbstract" id="oprx_WebBasedTechnologyAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="WebBasedTechnologyTextBlock" id="oprx_WebBasedTechnologyTextBlock" type="nonnum:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="WarrantsDisclouresAbstract" id="oprx_WarrantsDisclouresAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="WarrantsTextBlock" id="oprx_WarrantsTextBlock" type="nonnum:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="MajorCustomerAbstract" id="oprx_MajorCustomerAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="MajorCustomerTextBlock" id="oprx_MajorCustomerTextBlock" type="nonnum:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="BasisOfPresentationPolicyTextBlock" id="oprx_BasisOfPresentationPolicyTextBlock" type="nonnum:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="PrepaidExpensesTableTextBlock" id="oprx_PrepaidExpensesTableTextBlock" type="nonnum:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="ScheduleOfCapitalizedCostsInDevelopingWebBasedTechnologyTableTextBlock" id="oprx_ScheduleOfCapitalizedCostsInDevelopingWebBasedTechnologyTableTextBlock" type="nonnum:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="ScheduleOfShareBasedCompensationWarrantActivityTableTextBlock" id="oprx_ScheduleOfShareBasedCompensationWarrantActivityTableTextBlock" type="nonnum:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="ScheduleOfMajorCustomersIndividualRevenueTableTextBlock" id="oprx_ScheduleOfMajorCustomersIndividualRevenueTableTextBlock" type="nonnum:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="NatureOfBusinessDetailsTextualAbstract" id="oprx_NatureOfBusinessDetailsTextualAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="SummaryOfSignificantAccountingPoliciesTable" id="oprx_SummaryOfSignificantAccountingPoliciesTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem"/>
<element name="SummaryOfSignificantAccountingPoliciesLineItems" id="oprx_SummaryOfSignificantAccountingPoliciesLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="SummaryOfSignificantAccountingPoliciesDetailsTextualAbstract" id="oprx_SummaryOfSignificantAccountingPoliciesDetailsTextualAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="PrepaidLegalFees" id="oprx_PrepaidLegalFees" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item"/>
<element name="PropertyPlantAndEquipmentTextualAbstract" id="oprx_PropertyPlantAndEquipmentTextualAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="WebBasedTechnologyMember" id="oprx_WebBasedTechnologyMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="OptimizerxEhrIntegratedTechnologyMember" id="oprx_OptimizerxEhrIntegratedTechnologyMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="WebBasedTechnologyTextualAbstract" id="oprx_WebBasedTechnologyTextualAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="CapitalizedComputerSoftwareAmortizationPeriodDescription" id="oprx_CapitalizedComputerSoftwareAmortizationPeriodDescription" type="xbrli:stringItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="PatentAndTrademarksTextualAbstract" id="oprx_PatentAndTrademarksTextualAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="OptionsGrantedToAcquireExclusivePatentRightsShares" id="oprx_OptionsGrantedToAcquireExclusivePatentRightsShares" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="OptionsGrantedToAcquireExclusivePatentRightsValue" id="oprx_OptionsGrantedToAcquireExclusivePatentRightsValue" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item"/>
<element name="AdjustmentToDebtObligationPaymentToRelatedParty" id="oprx_AdjustmentToDebtObligationPaymentToRelatedParty" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item"/>
<element name="DeferredRevenueTextualAbstract" id="oprx_DeferredRevenueTextualAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="RelatedPartyTransactionsTextualsAbstract" id="oprx_RelatedPartyTransactionsTextualsAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="PreferredStockTextualAbstract" id="oprx_PreferredStockTextualAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="PlacementAgentsMember" id="oprx_PlacementAgentsMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="ThreeOfficersMember" id="oprx_ThreeOfficersMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="ConsultantMember" id="oprx_ConsultantMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="VicisMember" id="oprx_VicisMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="TwoOfficersMember" id="oprx_TwoOfficersMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="UnrelatedPartyMember" id="oprx_UnrelatedPartyMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="ShadronStastneyMember" id="oprx_ShadronStastneyMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="ConsultingAgreementMember" id="oprx_ConsultingAgreementMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="CapitalMarketsAdvisoryAgreementMember" id="oprx_CapitalMarketsAdvisoryAgreementMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="SeparationAgreementMember" id="oprx_SeparationAgreementMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="PurchaseAgreementMember" id="oprx_PurchaseAgreementMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="SecuritiesPurchaseAgreementMember" id="oprx_SecuritiesPurchaseAgreementMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="VicisCapitalAgreementMember" id="oprx_VicisCapitalAgreementMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="CapitalSupportAgreementOneMember" id="oprx_CapitalSupportAgreementOneMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="NewCapitalMarketsAdvisoryAgreementSharesIssuedFirstMember" id="oprx_NewCapitalMarketsAdvisoryAgreementSharesIssuedFirstMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="FormerExecutiveOfficerMember" id="oprx_FormerExecutiveOfficerMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="CommonStockTextualAbstract" id="oprx_CommonStockTextualAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="WarrantExercisePricePeriod" id="oprx_WarrantExercisePricePeriod" type="xbrli:durationItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="CommissionsPercentage" id="oprx_CommissionsPercentage" type="num:percentItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="PurchaseOfWarrants" id="oprx_PurchaseOfWarrants" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="StockIssuedDuringPeroidSharesCacelled" id="oprx_StockIssuedDuringPeroidSharesCacelled" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="StockRedeemedDuringPeriodValueOne" id="oprx_StockRedeemedDuringPeriodValueOne" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item"/>
<element name="TwoThousandThirteenPlanMember" id="oprx_TwoThousandThirteenPlanMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="StockOptionsTextualAbstract" id="oprx_StockOptionsTextualAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
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<element name="WarrantTwoMember" id="oprx_WarrantTwoMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentExpirationDate" id="oprx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentExpirationDate" type="xbrli:dateItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentWeightedAverageOutstandingAbstract" id="oprx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentWeightedAverageOutstandingAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
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<element name="ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentWeightedAverageGranted" id="oprx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentWeightedAverageGranted" type="num:perShareItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentWeightedAverageExpiration" id="oprx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentWeightedAverageExpiration" type="num:perShareItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
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<element name="OperatingLeasesTextualsAbstract" id="oprx_OperatingLeasesTextualsAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="CustomerOneMember" id="oprx_CustomerOneMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="CustomerTwoMember" id="oprx_CustomerTwoMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="ConcentrationRiskPercentageTotal" id="oprx_ConcentrationRiskPercentageTotal" type="num:percentItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="FederalIncomeTaxExpensesBenefitPermanentAndTimingDifferences" id="oprx_FederalIncomeTaxExpensesBenefitPermanentAndTimingDifferences" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item"/>
<element name="FederalIncomeTaxExpensesBenefitValueAllowance" id="oprx_FederalIncomeTaxExpensesBenefitValueAllowance" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item"/>
<element name="LdmGroupMember" id="oprx_LdmGroupMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="PdrNetworkMember" id="oprx_PdrNetworkMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="InstallmentOneMember" id="oprx_InstallmentOneMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="InstallmentTwoMember" id="oprx_InstallmentTwoMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="CommitmentsAndContingentLiabilitiesTextualAbstract" id="oprx_CommitmentsAndContingentLiabilitiesTextualAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="ContigentLiabilitiesRelatedToAuditFeesInPercentage" id="oprx_ContigentLiabilitiesRelatedToAuditFeesInPercentage" type="num:percentItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="ExistingShares" id="oprx_ExistingShares" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item"/>
<element name="InstallmentsPaymentsAgreement" id="oprx_InstallmentsPaymentsAgreement" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item"/>
</schema>
