Little is known about the association between homocysteine (Hcy) and asymptomatic CAS in the healthy population. The purpose of this study was to investigate the relationship between Hcy levels and asymptomatic CAS in a Chinese community population. The current study included 5393 participants who were age of 40 years or older, and free of stroke, transient ischemic attack, and coronary artery disease. Demographic and clinical variables were investigated, and the presence of CAS was assessed by Color Doppler Ultrasound. A multivariate logistic regression was used to examine the association between Hcy levels and asymptomatic CAS. 361 (6.69%) participants were diagnosed with asymptomatic CAS, who had higher Hcy levels compared with those without (p-value for trend = 0.0001). After adjusting other possible risk factors, Hcy > 19.3μmol/L was considered as an independent indicator of asymptomatic CAS (OR 1.53, 95%CI 1.05-2.23; p-value for trend = 0.0265), but with a difference between participants with diabetes and without [OR (95%CI): 2.89(1.02-8.22) vs. 1.42(0.95-2.12); P interaction < 0.05]. In this large-population, community-based study, Hcy is an independent indicator of asymptomatic CAS, especially in patients with diabetes.