Objective To compare the economic effectiveness of universal screening, high-risk population screening, and no screening strategies for thyroid disease prevention and control among pregnant women in China through cost-effectiveness analysis, providing evidence-based support for optimizing health policy decisions on prenatal thyroid disease screening. Methods Based on the characteristics of thyroid disorders during pregnancy, a combined decision tree and Markov model was developed to conduct a lifetime cost-effectiveness analysis across three strategies: no screening, high-risk population screening, and universal screening. Sensitivity analyses were performed on key parameters. Results Base-case analysis demonstrated that universal screening was the most cost-effective strategy when the World Health Organization (WHO)-recommended payment threshold of 1×gross domestic product (GDP) per capita was used, with an incremental cost-effectiveness ratio (ICER) of 20636.18 yuan per quality-adjusted life year (QALY) compared to no screening, followed by high-risk population screening (ICER=21071.71 yuan/QALY). The results of the sensitivity analysis showed a strong stability of the model. Conclusions Of the 3 screening programs for thyroid disease in pregnancy, universal screening is the most cost-effective when the WHO-recommended payment threshold of 1×GDP per capita is used.