Background. This study is a retrospective analysis of infections in patients supported by ventricular assist devices (VADs) as a bridge to cardiac transplantation. Methods. Infections were assigned to four classes. Class I were patient-related nonblood infections, class II were blood-borne infections, class III were percutaneous site infections, and class IV were infections of intracorporeal VAD components. Results. The cumulative number and incidence of infections were higher during the early VAD experience than in more recent patients (p < 0.05), although the cumulative number and incidence of class II and IV infections were similar in earlier and later patients. There were 28 serious (ie, class II and IV) infections in 9 patients who died, and 35 serious infections in 11 patients who survived until transplantation. Three of 4 patients with class IV infections died. A larger cumulative number of infections (ie, total class I-IV) was associated with more fungal isolates (p < 0.001) and more class II and IV infections (p < 0.02). Positive fungal cultures were obtained in 16 patients, but there were only 3 class III and 1 Class IV fungal isolates. Conclusions. Infection remains an important problem for patients with VADs. Bloodstream infections (class II) can often be controlled by appropriate therapy. However, intracorporeal device infections (class IV) are associated with substantial morbidity and mortality. Optimal implant techniques together with optimal wound care, appropriate use of prophylactic antibiotics, and avoidance of infection in indwelling catheters remain the most practical means for minimizing the risk of VAD infection.