Objectives. This study sought to assess the performance, effectiveness, and costs of a decentralized antenatal syphilis screening program in Nairobi, Kenya. Methods. Health clinic data, quality control data, and costs were analyzed. Results. The rapid plasma reagin (RPR) seroprevalence was 3.4%. In terms of screening, treatment, and partner notification, the program's performance was adequate. The program's effectiveness was problematic because of false-negative and false-positive RPR results. The cost per averted case was calculated to be US $95 to US $112. Conclusions. The sustainability of this labor-intensive program is threatened by costs and logistic constraints. Alternative strategies, such as the mass epidemiologic treatment of pregnant women in high-prevalence areas, should be considered.