The use of mycophenolate mofetil (MMF) in pancreas transplantation has increased graft survival and decreased the incidence of acute rejections episodes (ARE), regardless of the choice of calcineurin inhibitor. The combination of MMF with tacrolimus (TAC) is the most common protocol, it is considered the gold standard for new protocols. In the last few years, there have been reports of a small number of patients treated with sirolimus (RAPA), usually combined with TAC. Patient and pancreas survival rates as well as the incidence of ARE were similar to protocols with TAC and MMF. Twenty simultaneous pancreas and kidney (SPK) transplantations were performed using an immunosuppressive protocol of TAC, RAPA, and steroids (STE) after 2000. The incidence of ARE was 25%; all episodes responded to STE. Only 2 patients (10%) displayed hypercholesterolemia requiring treatment with statins. The use of RAPA as an alternative to MMF is promising, although presently one with limited experience. The combination of MMF and RAPA with or without a calcineurin inhibitor is an option to be evaluated in the future.