Background: Information on the impact of hormone replacement therapy (HRT) on carotid atherosclerosis is limited. Moreover, transdermal estrogens have not been investigated. Methods: We examined association of HRT use with ultrasonographically assessed carotid atherosclerotic plaque occurrence and mean common carotid artery intima-media thickness (CCA–IMT) progression. Within the Vascular Aging (EVA) Study, a community-based cohort, 815 postmenopausal women aged 59–71 have been followed during 4 years. Among these women, 166 had already used HRT. Results: Women who had ever used HRT experienced a lower occurrence of plaques (8.6 versus 19.1%, P=0.003). After adjustment for the main cardiovascular risk factors, odds-ratio for plaque occurrence was 0.41 (95% confidence interval 0.21–0.78, P=0.01) among ever users of HRT compared with never users. When transdermal route of estrogen administration was used, adjusted odds-ratio was 0.66 (95% confidence interval 0.47–0.99, P=0.04). The progression of IMT, which was measured at a plaque-free site and adjusted on initial levels of CCA–IMT did not differ between ever and never users of HRT. It was 0.011 mm per year among ever users and 0.012 mm per year among never users ( P=0.61). Conclusion: These data suggest that HRT use may prevent the development of atherosclerotic plaques in postmenopausal women, especially when estrogens are administered by transdermal route.