Infection is a problem in patients undergoing support with left ventricular assist systems. To better understand the nature of this problem, we retrospectively analyzed data on 56 patients supported by the HeartMate (Thermo Cardiosystems, Inc, Woburn, MA) left ventricular assist system. Infection was defined as fever >38°C, white blood count >12,000 cells/ml, and a need for antimicrobial therapy. Of the 56 patients, 25 (41%) had an infection. Device related infections (as determined by positive culture from driveline, housing, or inflow or outflow tract) occurred in eight patients (14.3%). The most common sites of infection were the respiratory system (42.4%), the central venous catheter (27.8%), and blood (18.3%). Of the positive cultures, 84% were bacterial and 16% fungal. There were no positive viral cultures. Positive cultures from left ventricular assist system related sites made up only 8.7% of the total. All but one of the patients with device related infections survived to transplantation. The long-term survival rate for patients in this group after transplantation was 77.8%. Two patients required surgical revision of the driveline because of infection. Both were free of infection postoperatively. Patients who stayed in the intensive care unit for longer periods had a greater risk of infection (uninfected, 35 days; infected, 78 days). In conclusion, although infection is a problem in patients undergoing support with left ventricular assist systems, it does not preclude survival to transplantation or alter the survival rate after transplantation.