The aim of the current study was to characterize the anti-HLA antibodies before and after pancreatic islet or pancreas transplantation. We assessed the risk of anti-donor specific antibody (DSA) sensitization in a single-center, retrospective clinical study at Geneva University Hospital. Data regarding clinical characteristics, graft outcome, HLA mismatch, donor HLA immunogenicity and anti-HLA antibody characteristic were collected. Between January 2008 and July 2014, 18 patients received islet transplants and 26 patients received a pancreas transplant. Eleven out of 18 patients (61.1%) in the islet group and 12 out of 26 patients (46.2%) in the pancreas group had anti-HLA antibodies. Six patients (33.3%) developed DSA against HLA of the islets and 10 patients (38.4%) developed DSA against HLA of the pancreas. Most of the DSA were at low level. Several parameters such as gender, number of transplantation, HLA mismatch, eplet mismatch and PIRCHE-II numbers, rejection and infection were analyzed. Only the number of PIRCHE-II was associated with the development of anti-HLA class II de novo DSA. Overall, the development of de novo DSA did not influence graft survival as estimated by insulin independence. Our results indicated that pre-transplant DSA at low levels, do not restrict islet or pancreas transplantation, especially islets transplantation (27.8% versus 15.4.%). de novo DSA do occur at a similar rate in both pancreas and islet transplant recipients mainly of class II and the immunogenicity of donor HLA is a parameter that should be taken into consideration. Low level DSA combined with an adequate immunosuppressive regimen and a close follow-up is acceptable in both pancreas and islet transplantation and are not associated with reduced graft survival or graft function.