Objective: We investigated effects of different regimens of hormone replacement therapy (HRT) on mammographic density. Methods: Ninety-five postmenopausal women, who were on different HRT regimens and completed their 4-year mammographic follow-up, were included into this retrospective and comparative study. Twenty-three of these women, who had surgical menopause, received conjugated equine estrogens (CEE) (Group I) only, 26 of them received CEE and continuous medroxyprogesterone acetate (MPA) (Group II), 21 women received CEE and cyclic MPA (Group III), and the remaining 25 women received tibolone (Group IV) therapy. Before commencing on HRT, a baseline high-resolution mammography was performed, and repeated at 6-12-month intervals during the period of 4-year follow-up. All mammographies were evaluated according to the Wolfe classification. Results: A diffuse increase in mammographic density was detected in five women (22%) in group I, nine women (35%) in group II, four women (19%) in group III, and two women (8%) in group IV. The increase in mammographic density was more common among women in group II than those in the other three groups. However, a statistically significant difference was found only between groups II and IV. Conclusions: Different HRT regimens have different effects on breast parenchymal density on mammography. Continuous combination HRT may be more commonly associated with an increase in breast density than other forms of HRT. © 2001 Elsevier Science Ireland Ltd. All rights reserved.