The Mexican Institute of Social Security (IMSS) provides care for more than 40% of the Mexican population. This report constitutes the first study of the incidence of congenital hypothyroidism (CH) in Mexican children. We performed a prospective study with a population base. CH screening began in 1997 with blood samples from the heel taken 72 h after birth; from 2000, the detection strategy was changed nationwide and blood samples were taken from the umbilical cord in all newborns for determination of thyroid-stimulating hormone (TSH) concentration. We evaluated the annual coverage. TSH concentration was measured by chemoluminescence; TSH values > or =30 microIU/mL in umbilical cord blood and 15 microIU/mL in capillary blood were considered positive cases and were confirmed through hormonal studies. The incidence and 95% confidence intervals [95% CI] were calculated. We found that coverage within the IMSS population was 53% from 1997 to 2000 and had increased to 95% by 2001. A total of 2,777,292 children from 2,975,157 births (93%) were studied between 2000 and 2004. Of these, 4050 had a high TSH concentration leading to suspicion of CH; CH was confirmed in 1286 (32%). The resulting incidence was 4.3/10,000 livebirths [95% CI 3.6, 5.1]. With the results obtained, we conclude that the IMSS strategy of CH screening at birth ensured 95% coverage of children in the system. The birth prevalence of CH reported is among the highest in the world.