Fifty-one simultaneous pancreas-kidney transplants (SPKT) were performed between 1988 and 2004 in patients of mean age 34 years and 23 years duration of diabetes treatment. All kidney and pancreas recipients were on maintenance hemodialysis therapy prior to SPKT. The pancreas with duodenal segment and the kidneys were harvested from cadaveric heart-beating donors. Cold ischemia time in UW solution varied from 4 to 14 hours (mean, 9 hours 35 minutes). Twenty patients had the duodenal segment sutured to the urinary bladder, and the remaining 31 grafts were drained to an isolated ileal loop. Quadruple immunosuppression was administered as well as an anticoagulant and antibiotic prophylaxis. Forty-nine patients (49/51, 96%) regained insulin independence in the immediate postoperative period; 44 (86%) displayed immediate graft function. The remaining patients experienced postoperative ATN, the longest duration was 18 days. Of 51 patients, 38 (14.5%) are alive (follow-up, 6 to 180 months), 26 (68.5%) have good pancreatic function, and 34 (89%), good kidney function. Nineteen (50%) patients regard their quality of life as improved compared to their pretransplant status, which is mainly attributed to being dialysis and insulin free. Of 19 patients, 14 (74%) reported measuring glycemia regularly due to fear of losing the pancreas graft. Of 19 persons, seven (37%) returned to work after transplantation. Four (8.3%) lost their kidney graft secondary to vascular complications (n = 2) or rejection (n = 2). Four pancreas grafts with bladder drainage required conversion to enteric drainage owing to persistent urinary infections or urinary fistulae. Fifteen (29%) patients lost their pancreatic grafts within 1 year of transplantation due to the following: vascular complications (n = 12), septic complications (n = 1), or rejection (n = 2). Thirteen patients died within 1 year after transplantation, 5 of septic complications, 5 of neuroinfection, 1 of pulmonary embolism, and 2 of myocardial infarction. In conclusion, SPKT is a successful treatment for diabetic nephropathy, burdened by the possibility of serious complications.