Our aim was to evaluate the prenatal diagnosis of β-thalassemia (β-thal) and other hemoglobinopathies in a region with high frequency. After detection by premarital or antenatal screening, 312 patients underwent 420 prenatal diagnostic procedures for 407 fetuses in a 10-year period. Fetal samples were collected by chorionic villi sampling (CVS) in the first trimester and amniocentesis and cordocentesis in the second trimester. Mutation analyses of β-globin and cytogenetic analyses were performed and the most common mutations detected were: IVS-I-110 (G>A), IVS-II-1 (G>A), IVS-I-6 (T>C) and IVS-II-745 (C>G). Hb S [β6(A3)Glu→Val, GAG>GTG)] was the most common hemoglobin (Hb) variant with a frequency of 6.3%. Among 407 fetuses, 105 (25.8%) were diagnosed as affected, while 201 (49.4%) were carriers and 101 (24.8%) were normal. Cytogenetic analyses revealed nine fetuses (2.3%) with numerical chromosomal abnormalities as regular or mosaicism. Prenatal diagnosis of common hemoglobinopathies is safe and effective. Performing cytogenetic analysis in excess fetal material is an acceptable option.