Introduction: Pancreatic islet allotransplantation represents a real therapeutic option in brittle T1DM. Clinical results have improved over the years even if long-term function of the transplantation remains limited (i.e. about 15% insulin-independence at 10 years after transplantation). It is well known that immunosuppressive strategy is one of the main determinants of the success of the procedure. Among the immunosuppressive protocols the administration of anti-thymocyte globulin (ATG) is recommended as immunosuppression induction therapy, before the islet infusion. The aim of our study was to investigate whether the first infusion of ATG administered before or during islet transplantation could influence the long-term function of the transplant itself. Materials and methods: We performed a retrospective single-center study on a sample of 15 patients (80% female, 20% male with mean age of 37.4 years) undergoing pancreatic islet transplantation at Niguarda Hospital in Milan. All the patients received immunosuppressive therapy consisting of induction treatment with anti-thymocyte globulin (6 mg/kg/day) followed by maintenance therapy with tacrolimus monohydrate (0.15 mg/kg), mycophenolate mofetil (2 g/day) and followed the same post-transplant management protocol. The endpoint of the study was to assess the achievement of long term insulin-independence, evaluated by serum C-peptide levels, comparing the two groups. The first one, consisting of ten patients, in which the infusion of the first dose of ATG had been completed before the start of the pancreatic islet transplantation, and the second group, consisting of five patients, in which the transplantation had taken place with the infusion of ATG still ongoing. Results: The follow-up in the evaluation of insulin-independence was on average 9 years (minimum 0.9 maximum 13.5 years). In the first group out of ten patients only one (10%) developed insulin-independence for two years and the other nine patients (90%) for less than one year. In the second group out of five patients everyone (100%) developed insulin-independence, 3 patients receiving a single infusion, 2 patients receiving a second infusion. The two groups of patients did not differ in the amount of islets per kg received (mean islet equivalent/kg 9503) and for all other variables analysed. Conclusions: Timing of ATG infusion appears to affect long-term insulin-independence in patients undergoing pancreatic islet allotransplantation.