To examine whether antecedent antimicrobial use influenced subsequent relative risk of urinary tract infection (UTI) in premenopausal women, data were analyzed from two cohorts of women observed prospectively for 6 months to determine risk factors for UTI. Using a Cox proportional hazards model to adjust for covariates, we found that 326 women in a University cohort and 425 women in a health-maintenance organization cohort were at increased risks for UTI (2.57 [95% confidence interval (CI), 1.24-5.32] and 5.83 [95% CI, 3.17-10.70], respectively) if antimicrobials had been taken during the previous 15-28 days but not during the previous 3, 7, or 14 days. The increased risks were noted both for women whose antimicrobial use was for treatment of a previous UTI and for women who received antimicrobials for other illnesses. These results suggest that recent antimicrobial use increases a woman's risk of UTI, perhaps by altering the indigenous urogenital flora and predisposing to vaginal colonization with uropathogens.