This prospective randomized single-blind placebo-controlled clinical trial was carried out to evaluate the effects of raloxifene administration on uterine and leiomyoma sizes in premenopausal women. Ninety healthy premenopausal women affected by asymptomatic uterine leiomyomas were enrolled and treated with raloxifene at the doses of 60 mg/d (group A), 180 mg/d (group B), or placebo (group C). The duration of the treatment was 6 cycles of 28 d each. At entry and after three and six cycles, uterine and leiomyoma sizes were measured by transvaginal ultrasonography. The difference between uterine and leiomyoma volumes (Delta size) was calculated in all subjects. The characteristics of the menstrual cycles and the side effects of the treatments were recorded using a daily diary. The severity of the uterine bleedings was assessed using a rank scale. Throughout the study, no significant changes were observed in uterine and leiomyoma size or in Delta size among the three groups and within each group of treatment. The length and severity of uterine bleedings was not significantly different between the three groups and within each group. In conclusion, raloxifene has no significant effect on uterine and leiomyoma size or on menstrual cycle in premenopausal women.