AIMS/HYPOTHESIS: The aim of this study was to compare the long-term outcomes--in terms of glucose control, renal function and procedure-related complications--of simultaneous islet-kidney (SIK) transplantation with those of simultaneous pancreas-kidney (SPK) transplantation in patients with type 1 diabetes mellitus. METHODS: HbA1c, need for insulin, GFR and complication rate were compared between 13 recipients of SIK and 25 recipients of SPK transplants at the same institution. The mean follow-up was 41 months. RESULTS: Two primary organ non-functions occurred in the SIK group. HbA1c did not differ at any time point during follow-up in the SIK group compared with the SPK group (mean during follow-up 6.3 vs 5.9%). Similarly, kidney function over time was not different between the two groups. A higher rate of insulin independence following SPK transplantation (after 1 year 96 vs 31% in the SIK group) was counterbalanced by a higher rate of serious adverse events (40% relaparotomies vs 0% in the SIK group). CONCLUSIONS/INTERPRETATION: The endogenous insulin production achieved by islet transplantation, combined with optimal insulin therapy, was sufficient for maintaining near-normal glucose levels. In terms of glucose control, islet transplantation provides results comparable to those achieved with pancreas transplantation. However, SPK results in a higher rate of insulin independence, albeit at the cost of more surgical complications. These results have led to a new paradigm in islet transplantation at our institution, where the primary goal is not insulin independence, but good glucose control and avoidance of severe hypoglycaemia.