BackgroundThe World Health Organisation (WHO) developed a comprehensive framework encouraging an integrated approach to achieve triple elimination of vertical transmission of HIV, syphilis, and hepatitis B in Asia. Current screening practices in Nepal show significantly lower coverage for syphilis and hepatitis B compared to HIV suggesting potential for integration. In this study, we aimed to model the cost-effectiveness of triple screening during antenatal care in Nepal.MethodsWe modelled maternal HIV, hepatitis B and syphilis cascade of care and their corresponding disease states using disease-specific Markov models over a 20-year horizon with a cycle length of one year. We compared dual integrated screening for HIV and syphilis and triple integrated screening for HIV, syphilis and hepatitis B with HIV screening only. Costs were estimated from a provider’s perspective. Results were presented as incremental cost-effectiveness ratios (ICERs). Univariable and probabilistic sensitivity analyses were conducted.FindingsOur modelling analysis showed that dual-integrated screening for HIV and syphilis was highly cost-effective when compared to current strategy of screening for HIV only (ICERs of US$18). Triple-integrated antenatal screening for HIV, syphilis and hepatitis B was highly cost-effective compared with dual-integrated strategy with an ICER of US$114. Moreover, 100% and 98% of the probabilistic sensitivity analysis estimates for dual- and triple-integrated screening were proven cost-effective, compared to HIV-only screening.InterpretationOur results support WHO recommendations for implementing integrated triple antenatal screening in Nepal and Asia more broadly, aiming to reduce maternal and neonatal morbidity through early detection and intervention.