Background: INTERMACS is a registry of FDA-approved durable mechanical circulatory support (MCS) devices used for the strategies of destination therapy (DT) and bridge to transplantation (BTT) or recovery. This study identifies predictors for death and transplantation based on initial results from INTERMACS. Methods: From June 23, 2006 to December 31, 2007, 420 patients from 75 institutions were prospectively entered into the INTERMACS database in which pre-implant data, indication for MCS device use, adverse events, demographics, hemodynamics, laboratory values and outcomes were recorded. Using competing outcomes methodology, risk factors were identified for the events of death and transplantation. Results: The devices included 314 left ventricular assist devices (LVADs), 5 right VADs (RVADs), 77 biventricular VADs (biVADs) and 24 total artificial hearts (TAHs) for a total of 497 pumps in 420 patients. Among the BTT patients at 6 months, 33% were alive with a device in place, 42% were transplanted, 22% had died, and 3% were explanted for recovery. Among the DT patients at 6 months, 68% were alive with a device in place, 5% were transplanted, 25% had died, and 2% were explanted for recovery. The risk factors identified for death across all patient groups include older age (relative risk [RR] = 1.41, p < 0.001), ascites (RR = 2.04, p = 0.003), increased bilirubin (RR = 1.49, p < 0.05) and INTERMACS Level 1 (cardiogenic shock) (RR = 1.59, p = 0.02). The most common causes of death were central nervous system (CNS) event (18.3% of deaths), multiple-organ failure (16.4%) and cardiac cause (right ventricular failure and arrhythmias, 15.4%). Conclusions: Cardiogenic shock, advanced age and severe right heart failure manifested as ascites or increased bilirubin are risk factors for death after MCS therapy. BTT patients who require biVAD support have a transplant rate similar to that of LVAD-only patients, but their mortality at 6 and 12 months exceeds that of LVAD-only patients. Consideration should be given to MCS referral before the sequelae of right ventricular failure dominate the advanced heart failure syndrome. © 2009 International Society for Heart and Lung Transplantation.