OBJECTIVES: To estimate the cost effectiveness of on-site antenatal syphilis screening and treatment in Mwanza, Tanzania. To compare this intervention with other antenatal and child health interventions, specifically the prevention of mother to child transmission of HIV (PMTCT). METHODS: The economic costs of adding the intervention to routine antenatal care were assessed. Cost effectiveness (CE) ratios of the intervention were obtained for low birth weight (LBW) live births and stillbirths averted and cost per DALY saved. Cost per DALY saved was also estimated for previous CE studies of syphilis screening. The CE of the intervention at different syphilis prevalence rates was modelled. RESULTS: The economic cost of the intervention is $1.44 per woman screened, $20 per woman treated, and $187 per adverse birth outcome averted. The cost per DALY saved is $110 with LBW as the only adverse outcome. When including stillbirth, this estimate improves 10-fold to $10.56 per DALY saved. The cost per DALY saved from all syphilis screening studies ranged from $3.97 to $18.73. CONCLUSIONS: Syphilis screening is shown to be at least as cost effective as PMTCT and more cost effective than many widely implemented interventions. There is urgent need for scaling up syphilis screening and treatment in high prevalence areas. The CE of screening interventions is highly dependent on disease prevalence. In combination, PMTCT and syphilis screening and treatment interventions may achieve economies of scope and thus improved efficiency.