To determine the causes of death in autosomal dominant polycystic kidney disease (ADPKD) patients and to examine whether the extrarenal manifestations of ADPKD influence the causes of death, the medical records of 129 patients who died between 1956 and 1993 were reviewed; 58% of the 129 patients had an autopsy performed. Seventy-seven percent died after reaching ESRD. The mean age at death increased from 51 yr for those who died before 1975 to 59 yr for those who died after 1975, reflecting the introduction of renal replacement therapies. The most common cause of death before 1975 was infection (30%), followed by uremia (28%) and cardiac disease (21%); after 1975, these were cardiac disease (36%) and infection (24%). Infection was equally prevalent before and after 1975, presenting as sepsis in 94% and directly relating to ADPKD in 47% of these patients. Underlying factors for cardiac death were cardiac hypertrophy, seen in 89% of all autopsied patients, and coronary artery disease, seen in 81%. A neurologic event was the cause of death in 12% of patients; these were ruptured intracranial aneurysm in 6%, hypertensive intracranial hemorrhage in 5%, and ischemic stroke in 1%. The mean age of those who died of ruptured intracranial aneurysm was 37 yr. No patient died of renal cancer. Liver cysts were the most common extrarenal manifestation, seen in 70% of the autopsied cases; cysts in other organs were very rare. Colonic diverticula were found in 21%. Thus, the renal and extrarenal manifestations of ADPKD are important contributors to morbidity and mortality.