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This study aims to retrospectively analyze the potential risk factors for uterine leiomyoma and prospectively examine whether these risk factors can increase the incidence of uterine leiomyoma.Women who attended our outpatient department from January 1, 2010 to December 31, 2010 were enrolled. General demographical characteristics, personal information, and living habits were collected. Univariate and multivariate logistic regression analyses were used to identify the potential risk factors. Follow-up was regularly conducted to complete the prospective analysis.A total of 1273 women were enrolled including 213 uterine leiomyomas (case group) and 1060 nonuterine leiomyoma women (control group). No statistical differences were found on the age, marital status, number and complication of pregnancy, frequent physical exercise, frequent alcohol consumption, and family history of uterine diseases between two groups (all P > .05). Mean body mass index (P = .043), high school education (P = .041), frequent smoking (P = .030), frequent caffeine consumption (P = .019), frequent milk or soybean consumption (P = .025), and frequent oral contraceptive use (P = .034) were statistically correlated with the onset of uterine leiomyoma. Multivariate analysis verified that frequent milk or soybean consumption (7.349 [5.081–9.454]; P = .039] and frequent oral contraceptive use (8.103 [4.486–12.583]; P = .018] were the independent risk factors for uterine leiomyoma.Frequent milk or soybean consumption and frequent oral contraceptive use are associated with a high risk of uterine leiomyoma, and proper education on the prevention of uterine leiomyoma is highly recommended in clinical practice.