OBJECTIVE: This study was undertaken to report on the benign gynecologic conditions occurring among women with an intact uterus at enrollment in the Breast Cancer Prevention Trial of the National Surgical Adjuvant Breast and Bowel Project. STUDY DESIGN: The incidence rates of several benign gynecologic conditions were determined and risks were compared among women receiving tamoxifen and those receiving placebo, based on risk ratios (RRs) with 95% CIs. Comparisons included stratification by menopausal status, body mass index, and history of estrogen use. RESULTS: Compared with women taking placebo, premenopausal women taking tamoxifen had a greater incidence of endometrial polyps (RR = 1.9, 95% CI = 1.55-2.41), leiomyomas (RR = 1.3, 95% CI = 1.14-1.55), endometriosis (RR = 1.9, 95% CI = 1.35-2.70), ovarian cysts (RR = 1.5, 95% CI = 1.20-1.78), and gynecologic surgical procedures, including hysterectomy (RR = 1.6, 95% CI = 1.29-1.88). Postmenopausal women taking tamoxifen also had an increased incidence of endometrial polyps (RR = 2.4, 95% CI = 1.76-3.24), leiomyomas (RR = 1.4, 95% CI = 1.04-1.80), endometriosis (RR = 1.9, 95% CI = 1.29-5.58), and gynecologic surgical procedures, including hysterectomy (RR = 2.2, 95% CI = 1.60-3.13), compared with women taking placebo. All women taking tamoxifen also had an increased incidence of simple endometrial hyperplasia without atypia (overall RR = 2.06, 95% CI = 1.64-2.60) compared with those taking placebo. CONCLUSIONS: Our results strongly support the estrogen agonist role of tamoxifen as the causative factor for the increased risk of endometrial polyps, leiomyomas, endometriosis, and endometrial hyperplasia among women taking this agent.