OBJECTIVE The objectives were to evaluate mammographic changes in breast density that are associated with raloxifene or hormone therapy and to compare the safety profiles of the two therapies. STUDY DESIGN Postmenopausal women older than 60 years who had a bone mineral density T-score of < or =-1 were assigned randomly to receive raloxifene hydrochloride 60 mg/day or continuous-combined hormone therapy that consisted of conjugated equine estrogen 0.625 mg/day plus medroxyprogesterone acetate 2.5 mg/day in a 1-year, open-label study. Radiologists who were blinded to the treatment assignment assessed the mammograms according to the American College of Radiology Breast Image Reporting and Data System breast density categories. Breast density changes were analyzed for treatment differences. RESULTS After 12 months of treatment, 0.9% of the women who received raloxifene had increased mammographic breast density compared with 27.4% of the women who received continuous-combined hormone therapy (P <.001). In the continuous-combined hormone therapy group, 77% of the women reported breast tenderness at any time during the study, compared to 22% of the women in the raloxifene group. CONCLUSION In postmenopausal women with low bone mass, raloxifene therapy for 12 months does not increase mammographic breast density, whereas continuous-combined hormone therapy substantially increases breast density in a significant number of women.