Autosomal dominant polycystic kidney disease (ADPKD) accounts for 8% to 10% of patients with end-stage renal disease (ESRD) in the United States and Europe. Progressive expansion of multiple bilateral renal cysts leads to massive enlargement of the kidneys and progressive renal failure. Extrarenal manifestations of ADPKD, such as liver cysts, intracranial aneurysms, cardiac valvular disease, and perhaps diverticulosis, have been documented extensively in cross-sectional studies, but little is known about their natural history. It is thought that extrarenal aspects of ADPKD contribute to increased mortality, yet survival on dialysis of the ADPKD population surpasses that of the general dialysis population. To address this issue, we analyzed the relative risk and causes of death after ESRD in ADPKD versus nondiabetic controls using data from the United States Renal Data System. Relative risk of death from any cause, including the major extrarenal manifestations of ADPKD, was determined as a function of ESRD treatment modality (dialysis or transplantation). We found a lower total mortality rate in ADPKD ESRD patients compared with nondiabetic control ESRD patients (relative risk of death in ADPKD = 0.57; P < 0.001). Mortality rates of extrarenal complications except for polycystic liver disease were similar or lower in ADPKD patients than in nondiabetic controls. Mortality secondary to extrarenal complications was substantially lower than that secondary to cardiovascular or cerebrovascular disease.