Background: Cardiovascular disease is the major cause of death in older women. Information on the relation of menopause and hormone replacement therapy with carotid atherosclerosis is limited. Methods and Results: We examined cross-sectionally the association of menopausal status, years since last menstruation, and hormone replacement therapy status with carotid artery intima-media thickness as determined by B-mode ultrasound. Female participants (n=5436) in the Atherosclerosis Risk in Communities Study without a history of symptomatic cardiovascular disease were included in the analyses. Menopause status in 45- to 54-year-old women who had never used hormone replacement therapy was not strongly associated with carotid intima- media thickness (mean=0.65 mm and 0.67 mm in premenopausal and postmenopausal women, respectively, adjusted for age, race, cigarette years of smoking, body mass index, sport index, systolic blood pressure, use of blood pressure medications, drinking status, diabetes, and education level). In postmenopausal women aged 55 to 64 years, women with ≤5 years since last menstruation had an adjusted average intima-media thickness (0.74 mm) comparable to those with >5 years since last menstruation (0.75 mm) (P > .05). Although hormone replacement therapy use was associated with a more favorable lipid and hemostasis profile than nonuse, its use was not associated with intima-media thickness in postmenopausal women aged 55 to 64 years (adjusted average=0.74 mm for current users of estrogen alone and ≃0.75 mm each for current users of estrogen plus progestin, former users, and never users). Conclusions: The data suggest that the well-known associations of hormone replacement therapy with reductions in atherosclerotic cardiovascular disease may be attributable more to acute physiological effects, such as hemodynamic changes or reduced thrombosis, than to atherosclerosis itself.