Liver transplantation is an established treatment for multiple end-stage liver diseases, yet little information is available on the autopsy-determined causes of death in liver transplant recipients. We undertook a retrospective study of the immediate causes of death in all liver transplant recipients who underwent autopsy at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, from January 1982 to January 1997. Infections were the most frequent cause of death, present in 64% of a total of 321 cases. Overall, the infections were bacterial in 48% of the cases, fungal in 22%, and viral in 12%. The ratio of infectious to noninfectious causes of death did not change significantly during the 15-year study period, and the relative percentages of bacterial, fungal, and viral infections showed relatively little variation on a year-to-year basis. Two-thirds of all infections occurred during the first 100 days post transplantation. A precipitous drop in the number of infections (and the number of deaths) occurred by Day 90. Other major causes of death included liver failure (12%), pulmonary failure (10%), multiple organ system (8%), and cardiovascular causes (6%). Infections were the most frequent cause of death in this study population, suggesting that improvement in the prevention and treatment of infections is an important way to improve survival of liver transplant recipients.