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To study the relation of maternal periconceptional vitamin use to the risk of a congenital urinary tract anomaly (CUTA), we conducted a case-control study using the Washington State Birth Defect Registry. We identified CUTA cases with no known chromosomal abnormality in seven counties in western Washington State occurring between January 1, 1990, and December 31, 1991. We randomly selected a sample, as controls, of all infants delivered in five large hospitals in King County who did not have a birth defect and who were born in the same year as the cases. About 55% of all infants in King County and a smaller proportion of infants in the other six counties are delivered in these five hospitals. We interviewed mothers of 118 cases and 369 controls to obtain information about their vitamin use during the pregnancy and during the year before the conception. After adjustment for maternal race, family income, county of maternal residence, and birth year, we found that women who used multivitamins during the first trimester had only 15% the risk of bearing a child with a CUTA compared with women who did not take vitamins [odds ratio (OR) = 0.15; 95% confidence interval (CI) = 0.05–0.43]. The reduction was smaller for use restricted to the second or third trimesters (OR = 0.31; 95% CI = 0.09–1.02). Among women who used vitamins during the first trimester, vitamin use before conception was not associated with any further reduction in the risk, nor did there appear to be an association with the amount or brand of vitamin used. Restricting the analysis to residents of King County did not change the results. Our results indicate that prenatal multivitamin use, particularly during the first trimester, may reduce the risk of a CUTA. Because all of the preparations taken by study participants contained many vitamins as well as folic acid, it was not possible to identify which one (or several) chemical(s) may have been responsible for the reduced risk of a CUTA.