ObjectiveUntreated maternal hypothyroidism during pregnancy can have adverse consequences on maternal health and child intelligence quotient (IQ). Our objective was to examine the cost-effectiveness of screening pregnant women for autoimmune thyroid disease.DesignWe developed a state-transition Markov model and performed a cost-effectiveness analysis of screening pregnant US women, aged 15–45 years, with no known history of thyroid disease, in the first trimester.MethodsThree strategies were compared: 1) no screening, 2) one-time screening using anti-thyroid peroxidase (anti-TPO) antibodies, and 3) one-time screening using TSH. Screening tests were added to the laboratory tests of the first prenatal visit. Abnormal screening tests were followed by further testing and subsequent thyroxine treatment of hypothyroid women.ResultsScreening pregnant women in the first trimester using TSH was cost-saving compared with no screening. Screening using anti-TPO antibodies was cost-effective compared with TSH screening with an incremental cost-effectiveness ratio of $15 182 per quality-adjusted life year. Screening using TSH remained cost-saving across a wide range of ages at screening, costs of treatment, and probabilities of adverse outcomes. The cost-effectiveness of anti-TPO screening compared with TSH screening was mostly influenced by the probability of diagnosing hypothyroidism in unscreened subjects or subjects with a normal screening test. Screening remained highly cost-effective in scenarios where we assumed no improvement of child IQ outcomes by levothyroxine treatment.ConclusionScreening all pregnant women for autoimmune thyroid disease in the first trimester is cost-effective compared with not screening.