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Introduction: Recent trials have shown significant improvement in outcome for patients suffering from acute ischemic stroke (AIS) when mechanical thrombectomy is added to the standard of care of IV tPA. In addition to the acute anti-platelet properties eptifibatide may also reduce acute inflammatory response following neurovascular intervention. Our goal was to evaluate the potential benefit of adding IV eptifibatide to mechanical thrombectomy and IV tPA.Methods: Patients who presented to a community based university affiliated comprehensive stroke center from 2012-2015 with AIS over a 2 year period were included in the study. Only patients who received thrombectomy after IV tPA were included. A subgroup of those patients also received IV eptifibatide as a continuous drip during and after the procedure. Details of bolus dosing and duration of treatment were documented. The initial NIH Stroke Score (NIHSS) and 24-hour NIHSS were compared between the two groups with paired samples t-test using SPSS Version 22.Results: A total of 866 patients were evaluated, and 139 met the study criteria. All patients received mechanical thrombectomy after IV tPA, but 70 also received a bolus dose of 135 mcg/kg of eptifibatide followed by 0.5 mcg/kg/min continuous drip. The mean duration of the drip was 23.8 minutes (SD 14.13). There were no significant differences in complication or hemorrhage rates between groups. The mean initial minus 24-hour NIHSS (Initial-24) for the patients receiving only IV tPA/thrombectomy was 1.6. Patients who also received eptifibatide had a mean Initial-24 of 3.6. The paired mean difference was 2 (95% CI .19-3.8; p=.03), favoring the addition of eptifibatide.Conclusion: The addition of eptifibatide bolus followed by a continuous drip for a mean of 24-hours to IV tPA/thrombectomy was associated with a significantly better 24-hour post-procedure outcome. The mechanism of action may be related to the suppression of inflammation and potential prevention of rethrombosis after treatment. No additional complications were noted with eptifibatide and patients tolerated it well. A larger prospective trial is warranted to corroborate our findings.