It has been established that mortality among US end-stage renal disease patients is higher than in many other developed countries. The explanation for this apparent difference in outcome results has caused considerable concern. The explanations for this difference are complex and could include differences in case mix as well as indices of severity of illness. To evaluate potential patient-based explanations for these discrepancies, we have evaluated existing reports as well as the available database at the Regional Kidney Disease Program at Hennepin County Medical Center, with particular emphasis on medical co-morbidity present in US end-stage renal disease patients. These data indicate that increasing age, a greater prevalence of diabetes mellitus patients, and a greater proportion of end-stage renal disease patients with complex medical co-morbidity contribute to the higher mortality seen in US patients receiving hemodialytic therapies.