Background. Successful islet allograft transplantation has been achieved worldwide. This study aimed at evaluating the relationship between peritransplant C-peptide (CP) values and long-term allograft function. Methods. We measured CP-to-glucose ratio (CPGR) in intraportal samples pre- and postinfusion, and in peripheral circulation at baseline pretransplant and at 1, 3, 6, 12, 72 hours, 1 week, and 15 and 30 days after first and second infusion in 13 islet allograft recipients. Peritransplant treatment included intravenous (IV) 5% dextrose in saline in all patients. We compared portal CPGR to insulin reduction (%) at 30 days after each infusion, and at 1 year after second infusion. Results. CPGR peaked between the immediate postinfusion and 3 hours and decreased at 12 hours. At 1 week, CPGR was 0.76 ± 0.45 and 1.44 ± 0.37 after first and second infusion, respectively. CPGR at 30 days after second infusion doubled compared to first infusion (P