OBJECTIVE In patients with type 1 diabetes and end-stage renal disease, combined transplantation of a kidney together with a pancreas or isolated pancreatic islets are options to improve glycemic control. The aim of this study was to compare their long-term outcome with regard to metabolic control and surgical complication rate, as well as function of the transplanted kidney. RESEARCH DESIGN AND METHODS We conducted a prospective cohort study in consecutive patients receiving either a pancreas or islet transplant simultaneously with or after kidney transplantation (simultaneous pancreas-kidney [SPK]/pancreas-after-kidney [PAK] or simultaneous islet-kidney [SIK]/islet-after-kidney [IAK] transplantation). RESULTS Ninety-four patients who had undergone SPK/PAK transplantation were compared with 38 patients who had undergone SIK/IAK transplantation over a period of up to 13 years. HbA1c levels declined from 7.8 ± 1.3% (62 ± 14 mmol/mol) to 5.9 ± 1.1% (41 ± 12 mmol/mol), and from 8.0 ± 1.3% (64 ± 14 mmol/mol) to 6.5 ± 1.1% (48 ± 12 mmol/mol), respectively, in the SPK/PAK and SIK/IAK groups (P < 0.001 for both) and remained stable during follow-up, despite a reduction in the rate of severe hypoglycemia by >90%. The 5-year insulin independence rate was higher in the SPK/PAK group (73.6 vs. 9.3% in the SIK/IAK group), as was the rate of relaparotomy after transplantation (41.5 vs. 10.5% in the SIK/IAK group). There was no difference in the rate of kidney function decline. CONCLUSIONS During a long-term follow-up, SPK/PAK transplantation as well as SIK/IAK transplantation resulted in a sustained improvement of glycemic control with a slightly higher glycated hemoglobin level in the SIK/IAK group. While insulin independence is more common in whole-organ pancreas recipients, islet transplantation can be conducted with a much lower surgical complication rate and no difference in kidney function decline.