BACKGROUND: Despite the beneficial effects of mechanical circulatory support (MCS), the majority of patients ultimately will have an adverse event. Although hemolysis is common among temporary devices, the incidence and clinical significance of hemolysis in patients managed with long-term, durable left ventricular assist device (LVAD) therapy is largely unknown. METHODS: Data were obtained from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). All adults who received a continuous-flow LVAD (CF-LVAD) between June 2006 and March 2012 were included. A hemolytic event was defined as a plasma-free hemoglobin >40 mg/dl in association with clinical signs of hemolysis occurring at least 72 hours after LVAD implant. Descriptive statistics, time-dependent analyses and multivariable modeling were employed for statistical purposes. RESULTS: A total of 4,850 patients followed for a mean of 11.1 months comprised the final study population. There were 340 hemolytic events in 260 patients. Freedom from hemolysis was 97% at 3 months, 94% at 1 year and 91% at 2 years. Mean time from implant to first hemolysis event was 7.4 months. Younger age (<60 years) was independently associated with greater hemolysis (p < 0.001). Thrombotic device malfunction, device exchange and mortality were all significantly higher after hemolysis, with the greatest risk for each occurring within 6 months. CONCLUSIONS: Hemolysis is not a rare event after CF-LVAD implantation and is associated with an early increase in morbidity and death. Future study should focus on other device and implant characteristics that may lead to hemolytic events, as well as appropriate strategies for managing affected patients.