Background and Objective: The safety of eptifibatide in combination with IV tPA for ischemic stroke has recently been demonstrated in the CLEAR-ER trial which used .6 mg/kg IV tPA plus eptifibatide (135 mcg/kg bolus and .75mcg/kg/min two-hour infusion) versus standard tPA (.9 mg/kg). Prior studies have also looked into the combination of intra-arterial (IA) tPA and eptifibatide at dosing and duration similar to cardiology literature. Our aim was to compare the safety and efficacy of eptifibatide after full dose IV tPA and endovascular treatment versus full dose IV tPA and endovascular treatment alone. Materials and Methods: We reviewed the records and procedure reports of patients who underwent endovascular treatment for ischemic stroke from 2010-2013 at a university affiliated comprehensive stroke center. Patients who received full dose IV tPA (.9 mg/kg) followed by endovascular treatment were compared with those who had the same treatment, but also received a bolus of 135 mcg/kg of eptifibatide followed by a .5 mcg/kg/min for 20 hours (based on IMPACT-II trial protocol). The initial and discharge NIH Stroke Scale as well as the discharge mRS (DCmRS) were evaluated. A DCmRS of 0 or 1 was considered a favorable outcome, and 2 or more was considered as a unfavorable. Initial stroke severity (NIHSS) was analyzed with logistic regression for baseline comparison and Fisher’s exact test were used for categorical data analysis. Results: We evaluated 2,016 patients with ischemic stroke, of which 230 received IV tPA and 91 (55% female) underwent endovascular treatment, 44 of them also received eptifibatide. Of the 44 patients who received eptifibatide (bolus and 20 hour infusion), 18% (n=8) had a favorable outcome, and in the group that did not receive eptifibatide , 9% (n=4) had a favorable outcome (OR=2.389, 95% CI 0.6645 to 8.589, p= 0.2217). Conclusion: Eptifibatide in combination with full dose IV tPA and endovascular treatment did not increase morbidity in our patient population, and may have improved outcome. Further, larger trials need to be conducted for more definitive results.