Sardinia, an Italian island in the Mediterranean sea with a population of 1,7 millions, has one of the highest incidence of β-thalassemia with 10-12% of carriers. Since 1977 we have been offering a capillary screening program and prenatal diagnosis to couples following non-directive genetic counselling. Thanks to the implementation of new molecular analysis methods, we shifted from prenatal diagnosis performed in 2nd trimester of pregnancy to 1st trimester. In order to avoid termination of pregnancy in case of affected fetuses following prenatal diagnosis we introduced preimplantation genetic testing, thus increasing notably the acceptance rate of antenatal screening and diagnosis by couples at high risk. In this paper, we report the continuous experience of our prenatal centre in Sardinia in 9,324 antenatal diagnoses of β-thalassemia, the accuracy and safety related to the prenatal procedures we employed, the termination of pregnancy rate and the couples’ acceptance of the different approaches as well as analyze the screening programs available to the Sardinian population. Molecular screening by Polymerase Chain Reaction (PCR) based methods, prenatal diagnosis by Chorionic Villous Sampling (CVS) with very low fetal loss rate (0,3%) and Preimplantation Genetic Diagnosis (PGD) were the most common techniques applied in our prenatal centre and they have brought to a drastical reduction of newborns affected by β-thalassemia to only 3-5 per year.