OBJECTIVES: Untreated syphilis in pregnancy is associated with adverse clinical outcomes to the infant. In Latin America, roughly three out of every ten women are not tested for syphilis during pregnancy. The objective of this analysis was to evaluate the cost-effectiveness, budget impact, and potential reduction in adverse pregnancy outcomes of antenatal syphilis screening using the recently introduced point of care immunochromatographic strip test across 20 countries in Latin America. METHODS: A previously published cost-effectiveness model was adapted to reflect the perspectives of the respective national health care systems. Clinical outcomes of infants born to syphilis-infected mothers on the endpoints of stillbirth, neonatal death and congenital syphilis were obtained from published sources. Treatment was assumed to consist of three injections of benzathine penicillin. Country-specific inputs included the antenatal prevalence of syphilis; annual number of live births; proportion of women with at least one antenatal care visit; per capita gross national income and estimated hourly nurse wages. RESULTS: In all 20 Latin American countries, syphilis screening is highly cost-effective with an weighted average cost/DALY averted of US$110 (range: US$10-US$308). Universal screening may reduce the annual number of stillbirths by up to 2,900, neonatal deaths by up to 1,100, the annual incidence of congenital syphilis by up to 1,450 and avert up to 130,000 DALYs at an incremental annual direct medical cost of US$ 5.9  million. The three relatively high prevalence countries of Brazil, Colombia and Haiti, account for over half of the total DALYs that could potentially be averted, whereas Chile and Cuba have already adopted universal screening. CONCLUSIONS: Use of ICS tests for antenatal syphilis screening is highly cost-effective in low and middle income countries in Latin America. Antenatal programs should either expand access or maintain full access to syphilis screening using the ICS test.