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  <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="ScheduleOfFutureMinimumLeasePaymentsTableTextBlock" type="dtr:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfFutureMinimumLeasePaymentsTableTextBlock"/>
  <xs:element name="ScheduleOfVestingOfCertainRestrictedStockUnitsTableTextBlock" type="dtr:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfVestingOfCertainRestrictedStockUnitsTableTextBlock"/>
  <xs:element name="LeasesDetailsScheduleofLeaseCostTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_LeasesDetailsScheduleofLeaseCostTable"/>
  <xs:element name="LeasesDetailsScheduleofLeaseCostLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_LeasesDetailsScheduleofLeaseCostLineItems"/>
  <xs:element name="LeasesDetailsScheduleofFutureMinimumLeasePaymentsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_LeasesDetailsScheduleofFutureMinimumLeasePaymentsTable"/>
  <xs:element name="LeasesDetailsScheduleofFutureMinimumLeasePaymentsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_LeasesDetailsScheduleofFutureMinimumLeasePaymentsLineItems"/>
  <xs:element name="EffectOfDilutiveStockOptionsWarrantsAndStockGrants" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_EffectOfDilutiveStockOptionsWarrantsAndStockGrants"/>
  <xs:element name="UnvestedRestrictedStockUnitAwards" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_UnvestedRestrictedStockUnitAwards"/>
  <xs:element name="WeightedAverageNumberOfSharesTotal" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_WeightedAverageNumberOfSharesTotal"/>
  <xs:element name="USHealthcareProvidersPercentage" type="dtr:percentItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_USHealthcareProvidersPercentage"/>
  <xs:element name="CashCashEquivalentsandShortTermInvestmentsDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_CashCashEquivalentsandShortTermInvestmentsDetailsTable"/>
  <xs:element name="CashCashEquivalentsandShortTermInvestmentsDetailsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CashCashEquivalentsandShortTermInvestmentsDetailsLineItems"/>
  <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="SharesOfCommonStockIssued" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SharesOfCommonStockIssued"/>
  <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="ReceivedProceeds" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_ReceivedProceeds"/>
  <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="RemainingExpenses" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_RemainingExpenses"/>
  <xs:element name="SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm2" type="xbrli:durationItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm2"/>
  <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="MarketbasedRestrictedStockUnits" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_MarketbasedRestrictedStockUnits"/>
  <xs:element name="ObligatedTermOfLease" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_ObligatedTermOfLease"/>
  <xs:element name="CompensationExpenseMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CompensationExpenseMember"/>
  <xs:element name="RevenueRecognizedAtAPointInTimeMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_RevenueRecognizedAtAPointInTimeMember"/>
  <xs:element name="RevenueRecognizedOverTimeMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_RevenueRecognizedOverTimeMember"/>
  <xs:element name="DocumentAndEntityInformationAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_DocumentAndEntityInformationAbstract"/>
</xs:schema>
