Douching has been linked to gonococcal or chlamydial cervicitis and pelvic inflammatory disease (PID) in retrospective studies. The authors conducted a 1999-2004 prospective observational study of 1,199 US women who were at high risk of acquiring chlamydia and were followed for up to 4 years. Cervical Neisseria gonorrhoeae and Chlamydia trachomatis were detected from vaginal swabs by nucleic acid amplification. PID was characterized by histologic endometritis or pelvic pain and tenderness plus one of the following: oral temperature >38.3°C, leukorrhea or mucopus, erythrocyte sedimentation rate >15 mm/hour, white blood cell count >10,000, or gonococcal/chlamydial lower genital tract infection. Associations between douching and PID or gonococcal/chlamydial genital infections were assessed by proportional hazards models. The 4-year incidence rate of PID was 10.9% and of gonococcal and/or chlamydial cervicitis was 21.9%. After adjustment for confounding factors, douching two or more times per month at baseline was associated with neither PID (adjusted hazard ratio = 0.76, 95% confidence interval: 0.42, 1.38) nor gonococcal/chlamydial genital infection (adjusted hazard ratio = 1.16, 95% confidence interval: 0.76, 1.78). Frequency of douching immediately preceding PID or gonococcal/chlamydial genital infection was not different between women who developed versus did not develop outcomes. These data do not support an association between douching and development of PID or gonococcal/chlamydial genital infection among predominantly young, African-American women.