The decision between a simultaneous pancreas-kidney (SPK) or kidney-alone (KA) transplant for the treatment of diabetic end-stage renal disease depends on the risk-versus-benefit of each procedure. In this study we compared the mortality, morbidity, graft function and acute rejection after 88 SPK and 65 KA transplants. All acute rejection episodes were biopsy-proven. Patient survival was higher in the KA group (KA 92%, SPK 83%) at 1 year, but similar in both groups at 5 years (SPK 78%, KA 71%). Whereas myocardial infarction accounted for a similar proportion of deaths in both groups, sepsis and surgical complications were more common causes of death in the SPK group. The majority of cardiovascular deaths occurred early in the SPK group compared to the KA group. Kidney graft survival was similar at 1 year (SPK 79%, KA 81%) and 5 years (SPK 66%, KA 59%). Pancreas graft survival at 1 and 5 years was 75% and 60% respectively. Biopsy-proven acute rejection occurred more frequently in the SPK group (SPK 63%, KA 46%). Morbidity was greater in the SPK group and included vascular (SPK 19%, KA 3%), non-infectious urologic (SPK 23%, KA 3%) and infectious complications (SPK 86%, KA 33%). The majority of complications in the SPK group were related to the pancreas allograft. In summary, SPK transplants were associated with an increased risk of early cardiovascular death, greater morbidity and more frequent biopsy-proven acute rejection episodes. However, kidney graft survival was not affected by the addition of the pancreas allograft.