ABSTRACT: Most studies on the relationship between bone mineral density and atherosclerosis have used dual-energy X-ray absorptiometry, but this method is relatively insensitive to bone geometry. The aim of this study was to investigate the relationship between bone area and indices of carotid and peripheral atherosclerosis. We studied 841 persons aged 65 years or older (women = 444, mean age 73.8 years; men = 397, mean age = 75.3 years) enrolled in the InCHIANTI study and free from active malignancies, chronic use of bisphosphonates or steroids, and estrogen replacement therapy. The tibial cortical and total cross-sectional area (CSA) were measured by peripheral quantitative computed tomography and their ratio was calculated (cortical/total cross-sectional area ratio, cCSA/tCSA); carotid plaques were screened by echography, and peripheral artery disease (PAD) was defined as an ankle/brachial index <0.9 or presence of intermittent claudication. No association between cCSA/tCSA and atherosclerosis was observed in men. In women, lower cCSA/tCSA was associated with both carotid plaques [odds ratio (OR) for lowest vs. best quartile = 2.09, 95 % confidence interval (CI) 1.2-3.68] and PAD (OR = 3.43, 95 % CI 1.58-8.12). After correction for potential confounders (age since menopause, body mass index, Parathyroid hormone, vitamin D, leptin, DHEA-S, testosterone, physical activity, chronic obstructive pulmonary disease, and reduced renal function), the association was not confirmed. According to partial logistic regression, the carotid plaque-cCSA/tCSA association, but not the PAD-cCSA/tCSA association, was mostly dependent on years since menopause. In women the association between osteoporosis and carotid plaques likely reflects hormonal deprivation, whereas that between osteoporosis and PAD seems multifactorial in origin.