Objectives: To determine the morbidity and mortality from radical cystectomy in a nationally representative population-derived sample. Complications after radical cystectomy have been reported from large single-institution series but population-based representative data are lacking. Methods: All patients undergoing radical cystectomy for bladder cancer were identified from the National Inpatient Sample data set of the Health Care Utilization Project (1998 to 2002). The prevalence of different complications coded according to the International Classification of Diseases, version 9, after cystectomy were determined. Independent hospital and patient-related factors associated with the occurrence of a complication were determined by logistic regression analysis. The prevalence of complication by type and frequency were compared with that in other large reported series. Results: The in-hospital mortality rate was 2.57%, and at least one complication other than death occurred in 28.4% of patients. These rates were comparable to those reported in published studies. Younger patients had a lower likelihood of complications. Younger patients and those undergoing cystectomy at large bed size, urban, teaching hospitals were less likely to have secondary complications after surgery, and younger patients, women, and those undergoing cystectomy at high-volume hospitals were less likely to have primary complications directly related to their surgery. Conclusions: The overall morbidity and mortality rates after radical cystectomy in a population-based sample were comparable to those reported from individual centers. Larger centers in urban locations may have lower complication rates but only hospitals performing a high volume of cystectomies were associated with fewer primary surgery-related complications.