BackgroundChlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are common sexually transmitted infections (STIs) associated with adverse outcomes, yet most countries do not test and conduct syndromic management, which lacks sensitivity and specificity. Innovations allow for expanded STI testing; however, cost is a barrier.MethodsUsing inputs from a pilot program in Botswana, we developed a model among a hypothetical population of 50,000 pregnant women to compare 1-year costs and outcomes associated with 3 antenatal STI testing strategies: (1) point-of-care, (2) centralized laboratory, and (3) a mixed approach (point of care at high-volume sites, and hubs elsewhere), and syndromic management.ResultsSyndromic management had the lowest delivery cost but was associated with the most infections at delivery, uninfected women treated, CT/NG-related low-birth-weight infants, disability-adjusted life years, and low birth weight hospitalization costs. Point-of-care CT/NG testing would treat and cure the most infections but had the highest delivery cost. Among the testing scenarios, the mixed scenario had the most favorable cost per woman treated and cured ($534/cure). Compared with syndromic management, the mixed approach resulted in a mean incremental cost-effectiveness ratio of $953 per disability-adjusted life years averted, which is cost-effective under World Health Organization's one-time per-capita gross domestic product willingness-to-pay threshold.ConclusionsAs countries consider new technologies to strengthen health services, there is an opportunity to determine how to best deploy resources. Compared with point-of-care, centralized laboratory, and syndromic management, the mixed approach offered the lowest cost per infection averted and is cost-effective if policy makers' willingness to pay is informed by the World Health Organization's gross domestic product/capita threshold.