OBJECTIVES: To evaluate the first prospective screening program in China for control of α and β-thalassemia in the population of pregnant couples. METHODS: During the period between January 1993 and December 2003, a hospital-based preventive program was conducted at the biggest birth center in Guangzhou, with 1/17 of all deliveries in this city referred annually by use of conventional heterozygote screening strategy in combination with the system of regular healthcare examination in pregnancy. RESULTS: The screened records included 49 221 pregnant women, and 4503 husbands of the pregnant women showed positive on the screening test. Of the at-risk couples, there were 198 for α-thal (4.4%) and 83 for β-thal (1.8%), respectively. Genetic counseling was offered to all at-risk couples and a successful prenatal diagnosis was performed for 269 out of 281 (95.7%) for α- or β-thal major, with the remaining 12 couples refusing to accept prenatal diagnosis. Out of 187 pregnancies at risk for homozygous α-thal and 82 at risk for β-thal major, 51 hydrops fetalis with Hb Bartʼs and 18 β-thal major were identified. All pregnancies with affected fetuses were voluntarily terminated, leading to a marked reduction of severe α- and β-thal births at this hospital since the program has been launched. CONCLUSIONS: Our hospital-based program proved to be highly effective in reducing severe thals in pregnant populations.