BACKGROUND It is not known how different steroid-free immunosuppressive combinations affect long-term kidney transplant function in recipients of simultaneous kidney and pancreas transplant (SPK). Here, we sought to evaluate, in SPK recipients, the impact on long-term renal allograft function of two Tac-based prednisone-free maintenance immunosuppressive protocols: tacrolimus (Tac)/mycophonelate mofetil (MMF) versus Tac/ sirolimus (SRL). METHODS In this single-center, retrospective, sequential study, we analyzed 59 SPK transplant patients with at median follow up of 5 years. All patients received induction therapy with thymoglobulin and maintenance immunosuppression with Tac/MMF (n=22) or Tac/SRL (n=37). There were no differences between the two groups in regards to age, gender, race, panel reactive antibodies, degree of mismatch, donor age, incidence of delay graft function, and Tac trough levels at different time points after transplantation. RESULTS Kaplan-Meier patient survival at 6 years after transplantation was not statistically different between the two groups. Rate of ACR was similar. Kidney survival, even if not statistically significant, was better in the Tac/MMF group than in the Tac/SRL (90.7% vs. 70.7%, P=0.09). The slope of glomerular filtration rate decline per month at 5 years after transplantation was not statistically different between the two groups. Both groups had the same decline over time in glomerular filtration rate of 0.40+/-0.06 mL/min/1.73/month. Pancreas survival at 6 years after transplantation was 100% in both treatment groups. CONCLUSIONS Our data suggest that, in SPK recipients, long-term kidney allograft survival and function are not statistically different. A trend toward an increased rate of renal allograft loss was found in the Tac/SRL-treated group.