The aim of this study was to assess safety and efficacy of islet transplantation after initial pancreas transplantation with subsequent organ failure. Patients undergoing islet transplantation at our institution after pancreas organ failure were compared to a control group of patients with pancreas graft failure, but without islet transplantation and to a group receiving pancreas re-transplantation. 10 patients underwent islet transplantation after initial pancreas transplantation failed and were followed for a median of 51 months. The primary end-point of HbA1c <7.0% and freedom of severe hypoglycemia was met by 9 out of 10 patients after follow-up after islet transplantation and in all 3 patients in the pancreas re-transplantation group, but by none of the patients in the group without re-transplantation (n=7). Insulin requirement was reduced by 50% after islet transplantation. Kidney function (eGFR) declined with a rate of -1.0ml±1.2 ml/min/1.73m2 per year during follow-up after islet transplantation, which tended to be slower than in the group without retransplantation (p=0.07). Islet transplantation after deceased donor pancreas transplant failure is a method that can safely improve glycemic control and reduce the incidence of severe hypoglycemia and thus, establish similar glycemic control as after initial pancreas transplantation, despite the need of additional exogenous insulin. This article is protected by copyright. All rights reserved.