INTRODUCTION: Preimplantation Genetic Diagnosis (PGD) is an alternative to prevent the affected pregnancies for the couples who are carrier for monogenic diseases. This study reports the experience of our Centre, from 1999 to 2004, in Preimplantation Genetic Diagnosis (PGD) for single gene disorders (SGD), describing strategies and overall outcome data of 222 PGD cycles performed on embryos of 158 couples for 22 different genetic conditions. MATERIALS and METHODS: The single gene defects investigated were autosomal dominant (n=14), autosomal recessive (n=133), or X-linked disorders (n=19). Fifty-five cycles were performed for SGD combined with HLA matching. Mutation analysis of gene regions affected by mutations was carried out using both minisequencing method or multiplex fluorescent PCR. RESULTS: A total of 1683 embryos were analysed by PCR amplification of 2955 blastomeres. Diagnosis was achieved for 1580 (93.9%) embryos, 380 of which were transferred to the patients in 186 cycles. Overall, 44 clinical pregnancies were achieved (23.7% per transfer), resulting in the birth of 33 healthy babies. CONCLUSIONS: The present results complement other similar experiences in the field and confirm the feasibility of PGD when applied in the context of a preventive genetic service.