The objective of the study was to determine the human teratogenic risk of vitamin A supplementation during pregnancy. Paired analysis of cases with congenital abnormalities and matched healthy controls was performed in the large population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1994. Of 35,727 pregnant women who had control infants without defects, 3399 (9.5%) were treated with vitamin A. Of 20,830 pregnant women who had case offspring with congenital abnormalities, 1642 (7.9%) were treated with vitamin A, a rate that is significantly lower than that of the control group (p < 0.001). The case-control pair analysis also showed a lower rate of vitamin A treatment during pregnancy and in the first trimester of gestation in most congenital abnormality groups. Thus, use of low or moderate doses of vitamin A (< 10,000 IU) during the first trimester of pregnancy (i.e., organogenesis) is not teratogenic but presents some protective effect to the fetus.