Current expansion of the recipient population and increased utilization of left ventricular assist devices as a bridge-to-transplantation have resulted in HLA sensitization becoming an increasingly important clinical problem in cardiac transplantation. We evaluated the impact of HLA sensitization and donor cause of death on survival in 500 cardiac transplant recipients. Donor cause of death was grouped into two categories, trauma and nontrauma. Panel reactive antibodies at the time of transplant were assayed and used as a marker for sensitization if more than 10%. Sensitized recipients had a poorer 1-year survival than those not sensitized (76 vs. 89%, respectively, P=0.2). Donor cause of death had an overall significant impact on survival with 1-year survival for recipients of trauma organs of 92 and 82% for recipients of nontrauma hearts (P=0.02). Trauma hearts transplanted into sensitized recipients yielded a survival of 93% at 1 year whereas if nontrauma donor hearts were transplanted into these recipients, survival was only 52% at 1 year, P<0.001. These intriguing results suggest that graft survival in HLA-sensitized recipients could be significantly improved through the use of hearts from trauma death donors.