Background: Continuous-flow left ventricular assist devices (LVAD) are increasingly being used in patients with end-stage heart failure and have largely replaced older generation pulsatile devices. While significant rates of infection have been reported in patients with pulsatile device support, incidence and outcomes of this complication for the continuous-flow device patients remain unknown. Methods: Between June 2005 and August 2009, 81 patients were implanted with continuous-flow LVADs at Washington University School of Medicine either as bridge to transplantation or as destination therapy. Outcomes of this study included incidence of postimplantation infection, types of infection, microbiologic profile, and association of postimplantation infections with clinical endpoints. Results: Forty-two patients (51.9%) had at least one type of infection on continuous-flow LVAD support with a mean follow-up period of 9.2 ± 9.2 months. Patients who had an infection on LVAD support had a significantly prolonged hospital stay (37.9 ± 32.0 versus 20.7 ± 23.0 days, p = 0.008) and a trend toward increased mortality (33.1% versus 18.7% at 2 years, respectively, log rank p = 0.102) compared with patients who did not. Subgroup analysis revealed that postimplantation sepsis was significantly associated with increased mortality in the continuous-flow LVAD cohort (61.9% versus 18.0% at 2 years, respectively, in septic and nonseptic patients, log rank p = 0.001). The majority of the sepsis cases occurred before hospital discharge, whereas most of the device related infections occurred after discharge. Resistant Staphylococcus and Pseudomonas species were the most common pathogens leading to device- and nondevice-related local infections. Development of driveline or pocket infection had no effect on survival in patients with continuous-flow assist device support (p = 0.193). Conclusions: Even though better clinical outcomes have been achieved with the newer generation continuous-flow devices, infection complicationsin particular sepsisare still a major risk for patients with continuous-flow LVAD implantation. Prevention strategies with aggressive medical and surgical management of infections may increase survival and decrease morbidity among continuous-flow LVAD patients.