Statement on the purpose of the study: PGD of single gene disorders, combined with Human Leukocyte Antigen (HLA) matching, represents one of the most recent applications in reproductive medicine. This strategy has emerged as a tool for couples at risk of transmitting a genetic disease to select unaffected embryos of a HLA tissue type compatible with that of an existing affected child. At delivering, stem cells from the newborn umbilical cord blood can be used to treat the affected sibling. Here we present the results of the application of a customised protocol on PGD of single gene disorders combined with HLA matching. Methods used: The PGD strategy involved a multiplex external/nested PCR allowing the simultaneous amplification of the causative mutations, STR markers linked to these regions for ADO detection, and a range of 10-15 informative HLA STR markers. Mutation analysis was carried out using the minisequencing technique. Summary of the results: Preimplantation HLA matching was performed on 41 cycles (37 for -thalassemia, 1 for Wiscott-Aldrich syndrome, 1 for Diamond-Blackfan anemia and 2 for leukaemia) from 31 couples overall, involving the testing of 341embryos in combination with a genetic disease, and of 22 embryos for HLA matching only. A reliable HLA genotype was achieved in 628/651 (96.4%) of the blastomeres analysed. Fifty-two (14.3%) HLA compatible embryos were identified, 39 (10.7%) of them resulted unaffected and 32 have been transferred back to patients. Five clinical pregnancies were obtained, 3 of them have been already born. Two pregnancies are still ongoing and were confirmed as healthy and HLA identical with the affected children by prenatal diagnosis. Conclusions: The current data confirm the feasibility of preimplantation HLA matching as a part of PGD, providing a realistic option for couples desiring an HLA-compatible child for the treatment of affected siblings.