Hemolysis is becoming increasingly recognized as a major complication of left ventricular assist device (LVAD) support. Data regarding risk factors, prevalence, and outcomes are limited. To better define the characteristics and prognosis of hemolysis, we present a retrospective case-control study of LVAD patients in our institution. A detailed record review was conducted of 18 patients supported with the HeartMate II (HMII; Thoratec Corp, Pleasanton, CA) who were diagnosed with hemolysis, and their data were compared with 82 patients who received an LVAD implant during the same period who did not develop hemolysis. Patients were excluded if they did not survive hospitalization at the time of LVAD implantation. The primary end points of this analysis were time to death and time to first hospitalization. Of 100 total patients, 18 HMII patients (18%) were diagnosed with hemolysis. Those with hemolysis were younger, had significantly higher lactate dehydrogenase and bilirubin levels, lower international normalized ratio, and no difference in cannula velocities by transthoracic echocardiography. Patient survival in the hemolysis group was markedly decreased at 1 year (38.9% vs 89.3%, p < 0.001), but no differences in hospitalization (p = 0.57) were observed. Partial to complete thrombosis was noted in all of the pumps at explant. These findings demonstrate that hemolysis is associated with high mortality, likely serving as a marker of pump thrombosis. Elevated lactate dehydrogenase and bilirubin levels are important indicators for hemolysis, and lower international normalized ratio may pre-dispose for this worrisome condition. Diagnosis should prompt clinicians to consider pump exchange or explant, listing for transplantation, or intensifying anti-coagulation.