Purpose: We evaluated the efficacy of a prophylactic antibiotic paste in reducing left ventricular assist device (LVAD) pocket infections. Methods: Starting in May 2001 all LVAD recipients were treated with prophylactic antibiotic paste consisting of vancomycin powder, thrombin spray, and microfibrillar collagen hemostat placed into the LVAD pocket at time of implantation. Patients were followed and pocket cultures obtained at three clinical endpoints: heart transplantation, explantation, or death. Pocket infection rates of treated patients were compared to historical controls. Results: The study consisted of 11 treated and 105 control patients. Mean age was 49 and 50, respectively (p = NS). Gender ratio was equal between the two groups. The number of patients with pocket infections for the treated group was significantly less than for the control (n = 0 (0%) vs n = 38 (36.2%), p=0.01). Overall mortality rate was greater in the non-treated group, however, this was not statistically significant (0% vs 18.1%, P=0.20). Time with device was significantly greater in the control as compared to the treated group (82.1±71.9 vs. 37.7±31.4 days, p = 0.05). Subdivided further, control patients with pocket infections had longer device time when compared to the treated group (93.7±71.1 vs 37.7±31.4 days, p = 0.02). We conclude that sterilization ot LVAD pocket at time of implantation using antibiotic paste decreases LVAD pocket infections.