BACKGROUND: Congenital cytomegalovirus infection is associated with an increased risk of congenital malformations and neonatal disability, resulting in reduced quality of life for both the child and the mother. Therefore, secondary prevention of congenital cytomegalovirus infection remains highly relevant. AIM: This work aimed to evaluate the cost-effectiveness of valacyclovir therapy for primary cytomegalovirus infection in pregnant women during the first trimester for the prevention of congenital cytomegalovirus infection. METHODS: A model-based analysis with a 5-year time horizon was conducted from a societal perspective. The effectiveness of the intervention was derived from previously published double-blind randomized controlled trial data including women with primary cytomegalovirus infection in the first trimester of pregnancy. The model accounted for the probability of disability in children with congenital cytomegalovirus infection due to severe sensorineural hearing loss and neurodegenerative disorders. The impact of congenital cytomegalovirus infection on maternal and child quality of life was consistent with previously published data. Costs and quality-adjusted life years were discounted at an annual rate of 3%. RESULTS: Valacyclovir therapy is expected to reduce the proportion of children with disability resulting from congenital cytomegalovirus infection from 4.8% to 1.4% among all women with primary cytomegalovirus infection in the first trimester. Over a 5-year period, life expectancy increased by 0.172 quality-adjusted life years (QALY), whereas government expenditures decreased by 25.8 thousand rubles per patient with primary cytomegalovirus infection in the first trimester. Sensitivity analysis confirmed the robustness of the findings. CONCLUSION: Under the adopted assumptions, secondary prevention of congenital cytomegalovirus infection through valacyclovir therapy in pregnant women with primary cytomegalovirus infection during the first trimester leads not only to reduced neonatal mortality and disability but also to decreased healthcare budget expenditures. © Eco-Vector, 2025.