Background. The University of Alabama at Birmingham experience with investigational ventricular assist devices (VADs) used as a bridge to transplantation has increased over the past several years; it now includes 27 VAD implantations with 13 VAD runs lasting for extended periods (ie, >30 days). A review of complications experienced by patients during extended VAD runs is warranted before the further development and testing of chronically implanted mechanical circulatory support devices. Methods. This study focuses on the infectious complications of extended VAD support; it includes 13 patients who were supported by either a Thoratec or HeartMate VAD for longer than 30 days pending cardiac transplantation. Infection was defined as any positive culture. The infections were classed according to site and severity as follows: class I were patient-related non-blood-borne infections, class II were blood-borne infections, class III were VAD percutaneous site infections, and class IV were infections of the blood-contacting surfaces or intracorporeal components of the VAD. Results. The 8 Thoratec and 5 HeartMate patients were supported for a total of 1,648 days with a range of 33 to 279 days per patient. Every patient had at least one infection; however, there were 6 patients who had no class II or IV infections during the period of support. One of these 6 patients died of a stroke, whereas the other 5 patients survived VAD support. No trends were identified for a change in the cidence of bacterial compared with fungal infections during the course of VAD support. There was no trend for a greater number of infections in patients who died during VAD support compared with those who survived. Neither class II nor IV infections precluded transplantation. Three patients died during VAD support; 1 died as a direct consequence of fungal infection. Eight patients received transplants. One patient had an unanticipated recovery of cardiac function and the VAD was removed. Support in 1 patient is ongoing. Conclusions. Infection during VAD support pending cardiac transplantation is an important cause of morbidity and mortality in patients maintained for longer than 30 days by circulatory assist. Infectious complications will probably be a prominent component of the risk associated with the use of chronically implanted mechanical circulatory assist devices and will likely have an important effect on the quality of life experienced by these patients.