Left ventricular assist device thrombosis is a rare but potentially lethal complication of mechanical circulatory support. Here, we present a case of successful treatment of a suspected HeartMate II thrombosis with the glycoprotein IIb/IIIa inhibitor, eptifibatide. The patient presented with signs and symptoms of heart failure, along with acute kidney injury and hemolytic anemia that did not respond to diuresis, inotrope support, or anticoagulation. Treatment with eptifibatide resulted in marked clinical and hemodynamic improvement within 24 hrs. The patient was transitioned to clopidogrel and discharged without further incident. Eptifibatide may represent a potential therapeutic option for patients with device thrombosis.