In patients receiving left ventricular assistance for end-stage heart failure, pump-related thrombosis is a potentially fatal complication that may manifest as hemolysis and abnormally high pump power consumption. The optimal approach to treat this complication is unclear, especially in patients who are not heart transplant candidates or who have a high surgical risk. We report the successful use of direct thrombolytic therapy for recurrent hemolysis and thrombosis-related pump failure in a patient with the HeartWare ventricular assist device (HVAD), a third-generation, centrifugal flow pump. We know of only one previous case in which direct thrombolytic therapy has been used to treat the failure of a third-generation device. On the basis of our experience in the present case, we believe that direct thrombolytic therapy is a feasible option in these patients.