BACKGROUND: The menopausal transition is characterized by increased cardiovascular risk, weight gain, and increased adipos-ity for many women. The adipose-derived secretory proteins adiponectin and leptin are associated with insulin resistance, metabolic syndrome, and cardiovascular disease but their role in subclinical atherosclerotic disease is unclear. This cross-sectional study evaluated the associations of adiponectin and leptin with carotid artery intima-media thickness, adventitial diameter, presence of carotid plaques, and brachial-ankle pulse wave velocity (baPWV) in women aged 54 to 65 years. METHODS AND RESULTS: Participants were 1399 women from SWAN (Study of Women’s Health Across the Nation), a community-based study of women transitioning through menopause. Carotid ultrasound and baPWV measures were obtained at SWAN follow-up visits 12 or 13, when 97% of participants were post-menopausal. Adipokines were assayed from serum speci-mens obtained concurrently at these visits. Linear and logistic regression models were used to evaluate adiponectin or leptin, both log-transformed attributable to skewness, in relationship to carotid artery intima-media thickness, adventitial diameter, baPWV, and presence of carotid plaque. Covariates included age, race, study site, smoking, alcohol use, obesity, cardiovascular disease risk factors, and menopausal status. Lower levels of adiponectin were related to greater carotid artery intima-media thickness, wider adventitial diameter, and faster baPWV; associations were attenuated after adjusting for cardiovascular disease risk factors. Higher levels of leptin were associated with greater carotid artery intima-media thickness and wider adventitial diameter in minimally and fully adjusted models, and contrary to expectation, with slower baPWV, particularly among women with diabetes mellitus or obesity. CONCLUSIONS: Adiponectin and leptin are 2 important inflammatory pathways that may contribute to adverse subclinical cardiovascular disease risk profiles in women at midlife.