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<link:definition>002 - Statement - Consolidated Balance Sheet</link:definition>
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<link:definition>003 - Statement - Consolidated Balance Sheet (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>009 - Disclosure - Prepaid Expenses</link:definition>
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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: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:definition>014 - Disclosure - Related Party Transactions</link:definition>
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<link:definition>015 - Disclosure - Common Stock</link:definition>
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<link:definition>016 - Disclosure - Preferred Stock</link:definition>
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<link:definition>017 - Disclosure - Stock Options</link:definition>
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<link:definition>019 - Disclosure - Operating Leases</link:definition>
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<link:definition>020 - Disclosure - Major Customers</link:definition>
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<link:definition>021 - Disclosure - Income Taxes</link:definition>
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<link:definition>022 - Disclosure - Commitments and Contingent Liabilities</link:definition>
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<link:definition>023 - Disclosure - Retirement Plan</link:definition>
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<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>024 - Disclosure - Subsequent Events</link:definition>
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<link:usedOn>link:calculationLink</link:usedOn>
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<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>
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<link:definition>026 - Disclosure - Summary of Significant Accounting Policies (Tables)</link:definition>
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<link:usedOn>link:definitionLink</link:usedOn>
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<link:definition>027 - Disclosure - Prepaid Expenses (Tables)</link:definition>
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<link:definition>028 - Disclosure - Property and Equipment (Tables)</link:definition>
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<link:usedOn>link:calculationLink</link:usedOn>
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<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>
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<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:definition>031 - Disclosure - Stock Options (Tables)</link:definition>
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<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>032 - Disclosure - Warrants (Tables)</link:definition>
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<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>033 - Disclosure - Operating Leases (Tables)</link:definition>
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<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>034 - Disclosure - Major Customers (Tables)</link:definition>
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<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>035 - Disclosure - Income Taxes (Tables)</link:definition>
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<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>036 - Disclosure - Nature of Business (Details)</link:definition>
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<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>
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<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>
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<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>
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<link:definition>040 - Disclosure - Property and Equipment (Details)</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
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<link:definition>041 - Disclosure - Property and Equipment (Details Textual)</link:definition>
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<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>042 - Disclosure - Web Based Technology (Details)</link:definition>
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<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>043 - Disclosure - Web Based Technology (Details Textuals)</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/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>
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<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>
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<link:definition>046 - Disclosure - Deferred Revenue (Details)</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
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<link:definition>047 - Disclosure - Related Party Transactions (Details)</link:definition>
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<link:usedOn>link:definitionLink</link:usedOn>
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<link:definition>048 - Disclosure - Common Stock (Details)</link:definition>
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<link:usedOn>link:definitionLink</link:usedOn>
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<link:definition>049 - Disclosure - Preferred Stock (Details)</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
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<link:definition>050 - Disclosure - Stock Options (Details)</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
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<link:definition>051 - Disclosure - Stock Options (Detail Textuals)</link:definition>
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<link:usedOn>link:definitionLink</link:usedOn>
<link:usedOn>link:calculationLink</link:usedOn>
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<link:definition>052 - Disclosure - Warrants (Details)</link:definition>
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<link:usedOn>link:definitionLink</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>
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<link:roleType roleURI="http://OPRX/role/WarrantsDetailsTextuals" id="WarrantsDetailsTextuals">
<link:definition>054 - Disclosure - Warrants (Details Textuals)</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/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>
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<link:definition>056 - Disclosure - Major Customers (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/MajorCustomersDetailTextuals" id="MajorCustomersDetailTextuals">
<link:definition>057 - Disclosure - Major Customers (Detail Textuals)</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/IncomeTaxesDetails" id="IncomeTaxesDetails">
<link:definition>058 - Disclosure - Income Taxes (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/IncomeTaxesDetails1" id="IncomeTaxesDetails1">
<link:definition>059 - Disclosure - Income Taxes (Details 1)</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
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<link:roleType roleURI="http://OPRX/role/IncomeTaxesDetailTextuals" id="IncomeTaxesDetailTextuals">
<link:definition>060 - Disclosure - Income Taxes (Detail Textuals)</link:definition>
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<link:usedOn>link:definitionLink</link:usedOn>
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<link:definition>061 - Disclosure - Commitments and Contingent Liabilities (Details)</link:definition>
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<link:usedOn>link:definitionLink</link:usedOn>
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<link:definition>062 - Disclosure - Retirement Plan (Details)</link:definition>
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<link:usedOn>link:definitionLink</link:usedOn>
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<link:definition>063 - Disclosure - Subsequent Events (Details)</link:definition>
<link:usedOn>link:presentationLink</link:usedOn>
<link:usedOn>link:definitionLink</link:usedOn>
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<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/2015-01-31" schemaLocation="http://xbrl.fasb.org/us-gaap/2015/elts/us-gaap-2015-01-31.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/2013-01-31" schemaLocation="http://xbrl.sec.gov/country/2013/country-2013-01-31.xsd"/>
<import namespace="http://xbrl.sec.gov/currency/2014-01-31" schemaLocation="http://xbrl.sec.gov/currency/2014/currency-2014-01-31.xsd"/>
<import namespace="http://xbrl.sec.gov/exch/2015-01-31" schemaLocation="http://xbrl.sec.gov/exch/2015/exch-2015-01-31.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"/>
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<element name="SummaryOfSignificantAccountingPoliciesLineItems" id="oprx_SummaryOfSignificantAccountingPoliciesLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" />
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<element name="PropertyPlantAndEquipmentTextualAbstract" id="oprx_PropertyPlantAndEquipmentTextualAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" />
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<element name="NewCapitalMarketsAdvisoryAgreementSharesIssuedFirstMember" id="oprx_NewCapitalMarketsAdvisoryAgreementSharesIssuedFirstMember" type="nonnum:domainItemType" 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="CommissionsAndExpensesDescription" id="oprx_CommissionsAndExpensesDescription" type="xbrli:stringItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" />
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<element name="PurchaseOfWarrants" id="oprx_PurchaseOfWarrants" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" />
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<element name="DebtRedemptionLongtermDebtAmount" id="oprx_DebtRedemptionLongtermDebtAmount" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" />
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