BACKGROUND Untreated maternal syphilis can result in the fetuses being infected. Severe adverse pregnancy outcomes include stillbirth, perinatal death, low birth weight, and congenital syphilis (CS). The World Health Organization has already classified global elimination of CS as a priority. However, this preventable disease is still threatening people's health in the world. METHODS A Programme of Prevention of Mother-to-Child Transmission of Syphilis in Shenzhen was launched in 2002. All pregnant women in Shenzhen were screened for syphilis by serological methods at their first prenatal care visit. The infected individuals were treated with 3 weekly injections of 2.4 million units of benzathine penicillin. The babies were followed up until 18 months old to diagnose CS. RESULTS Up to 2011, the Programme of Prevention of Mother-to-Child Transmission of Syphilis in Shenzhen screened 2,077,362 pregnant women and intervened in 7668 mothers infected with syphilis. The screened rate among pregnant women increased from 89.8% in 2002 to 97.4% in 2011. The proportion of those having adverse pregnant outcomes (including spontaneous abortion, premature delivery, and stillbirth) decreased from 27.3% in 2003 to 8.2% in 2011. The incidence of CS decreased from 115/100,000 in 2002 to 10/100,000 (live births) in 2011. CONCLUSIONS In 2002, in the face of rising CS numbers, Shenzhen adapted a syphilis control program that involved cost-free testing for pregnant women, commitment and collaboration at multiple levels of the health system, and strong supervision and government guidance. Local program and surveillance data suggest that the program has been very successful in reducing CS incidence.