In patients with symptomatic coronary heart disease, skin cholesterol (SC) content is associated with the presence and extent of coronary artery disease; however, its relation to subclinical arterial disease in asymptomatic patients is unknown. The purpose of this study was to determine the relations between SC and carotid intima-media thickness (CIMT) in asymptomatic subjects across a wide range of cardiovascular risk. SC was measured using a noninvasive assay. CIMT and carotid plaque presence were determined by high-resolution B-mode ultrasound. Associations among SC, CIMT, carotid plaque presence, and cardiovascular risk factors were evaluated by multivariable logistic regression analyses. SC and CIMT were measured in 565 asymptomatic subjects (57 ± 10 years of age, 38% women) from 6 sites in North America. The mean Framingham 10-year cardiovascular risk was 8.4 ± 7.2%. A 10-U increase in SC was associated with a 12% increase in the odds of having increased CIMT (p = 0.006) and a 15% increase in carotid plaque presence (p = 0.002). Odds ratios (95% confidence intervals) associated with SC >110 U were 2.19 (1.25 to 3.85, p = 0.006) for increased CIMT and 2.89 (1.61 to 5.19, p <0.001) for carotid plaque presence. In conclusion, SC identified the presence of advanced subclinical atherosclerosis. The relations among increasing SC, increasing CIMT, and carotid plaque presence were consistent across all levels of cardiovascular risk and were independent of cardiovascular risk factors. SC may be a useful test for cardiovascular risk prediction.