Objective: The estrogenicity of dietary soy may increase the risk of diseases, such as uterine leiomyoma and endometriosis, which originate from uterine tissue and are predominant indications for hysterectomy. We sought to determine whether soy product intake is associated with an increased risk of premenopausal hysterectomy. Design: Prospective cohort study. Setting: Takayama City, Gifu, Japan. Subjects: A cohort of 1172 female residents randomly selected from participants in the Takayama Study who were aged 35-54 and premenopausal at the time they entered the study in 1992. Measurements: Diet including soy product and isoflavone intake was assessed by a validated semiquantitative food frequency questionnaire at baseline. Information on the onset of menopause and hysterectomy were obtained by a follow-up mail questionnaire in 1998. Results: During the 6 y study period, 31 women underwent premenopausal hysterectomies. The second tertile of isoflavone intake was significantly associated with an decreased risk of premenopausal hysterectomy compared to the lowest tertile of intake after controlling for age and total energy (rate ratio = 0.35, 95% confidence interval 0.13-0.97), although the dose-response relationship was not statistically significant. Conclusions: It is possible that soy product intake may be inversely associated with diagnoses leading to hysterectomy. Future studies focusing on specific diseases will be required to examine this possibility.