Left ventricular assist devices (LVADs) have been used effectively as a "bridge" to cardiac transplantation and as destination therapy in patients with advanced heart failure. Ventricular arrhythmias (VAs) have been reported to occur in LVAD-supported patients, although their incidence, risk factors, and clinical significance have not been characterized. In this study, 111 patients who received LVAD support as a bridge to cardiac transplantation at the University of Pittsburgh Medical Center from January 1987 to June 2001 were evaluated. Clinically significant VA was defined as ventricular fibrillation, sustained ventricular tachycardia, or nonsustained ventricular tachycardia with symptoms requiring antiarrhythmic therapy. Patients were grouped on the basis of the presence or absence of VAs. VAs occurred in 24 patients (22%) during device support. Ischemic heart disease was the cause of heart failure in 71% of patients (17 of 24) in the VA group and 45% of patients (39 of 87) in the group without VAs (p <0.05). The mortality rate was significantly higher (p <0.001) during LVAD support in the group with VAs (33%) compared with the group without VAs (18%). In the group with VAs, the early (<or=1 week) occurrence of VAs was associated with a significantly higher (p <0.001) mortality rate (54%) compared with late (>1 week) occurrence (9%). In conclusion, although clinically significant VAs occur in patients with heart failure receiving LVAD support, the overall incidence is low. VAs are more frequent in patients with ischemic heart failure, and their occurrence is associated with greater mortality. The occurrence of VAs early after LVAD implantation, in particular, predicts a higher mortality rate.