Hemoglobinopathies are the most frequent indications for preimplantation genetic diagnosis (PGD), allowing couples at-risk of bearing offspring with thalassemia and sickle cell disease to reproduce without fear of having an affected child. The present experience includes PGD for sickle cell disease, α- and β-thalassemia (α- and β-thal). We present here the results of the world's largest experience of over 395 PGD cycles for hemoglobin (Hb) disorders, resulting in the birth of 98 healthy, hemoglobinopathy-free children, with seven pregnancies still ongoing. One-third of these cases were performed in combination with HLA typing, allowing the birth of unaffected children who were also HLA identical to the affected siblings with hemoglobinopathies in these families, with successful or pending stem cell transplantation in a dozen of them. The results show that PGD is presently a practical approach for prevention of hemoglobinopathies, gradually also becoming a useful approach to improving access to HLA-compatible stem cell transplantation for this group of diseases.