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Objective: To assess the cost-effectiveness of modifying current antenatal screening by adding first trimester structural anomaly screening to standard of care second trimester anomaly screening., Design: Health economic decision model., Setting: National Health Service (NHS) in England and Wales., Population: Pregnant women attending for first trimester antenatal screening., Methods: The decision model estimated pregnancy outcomes (maternal and foetal) and 20-year costs for current screening practice and for a policy adding a protocol screening for eight major structural anomalies to the current first trimester ultrasound scan. Event probabilities, costs, and outcomes for the model were informed by meta-analyses, published literature, and expert opinion., Main Outcomes Measures: Expected numbers of pregnancy outcomes, healthcare costs, and maternal quality-adjusted life years (QALYs). Estimation of the incremental cost-effectiveness ratio (ICER), likelihood of cost-effectiveness, and a value of information (VoI) analysis assessing if further research is needed before making a decision about screening., Results: First trimester anomaly screening increased mean per woman costs by £11 (95% CI £1-£29) and maternal QALYs by 0.002065 (95% CI 0.00056-0.00358). The ICER was £5270 per QALY and the probability of cost-effectiveness at a willingness to pay value for a QALY of £20 000, exceeded 95%. VoI analysis showed further research would be unlikely to represent value for money. The protocol would likely lead to a reduction in infant healthcare costs and QALYs., Conclusions: A protocol to screen for eight major structural anomalies during the first trimester appears to represent value for money for the NHS. The opposing implications for mothers and infants, however, raise complex, challenging, and sensitive issues., (© 2025 The Author(s). BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)