Objective: Cardiovascular disease (CVD) occurs frequently and may progress more rapidly in overt hypothyroidism (OVH). However, the role of mild thyroid failure as a risk factor for CVD is not clear. This study is aimed at exploring the association between subclinical hypothyroidism (SCH) and coronary artery disease (CAD), as detected by cardiac computed tomography (CT), in apparently healthy subjects. Subjects and methods: We retrospectively enrolled 2404 asymptomatic subjects who underwent cardiac CT with an intermediate to high risk (Framingham 10-year risk R10%) of developing CAD but with no known CAD or thyroid disease. Coronary artery calcium score (CACS) was assessed by calcium scan, and the presence of the plaques (CAD), with R50% stenosis being indicative of obstructive CAD, was assessed by coronary CT angiography. Results: Of the 2404 subjects, 2355 subjects were euthyroid (Eu; 53G9 years, 83 females) and 49 had SCH (58G12 years, seven females). CAD and CACS O100 were more prevalent in SCH subjects than in Eu subjects (Eu vs SCH: CAD, 948 (40.6%) vs 31 (63.3%), PZ0.002; CACS O100, 239 (10.3%) vs 10 (20.4%), PZ0.031). SCH was also an independent risk factor for CAD after a multivariate analysis (odds ratio: 2.125, 95% confidence interval: 1.049-4.307, PZ0.036). Conclusions: SCH subjects who were at an intermediate-to-high risk of developing CAD were significantly more likely to exhibit occult CAD than Eu subjects, especially in men with SCH. These findings suggest that mild thyroid failure also independently contributes to the development of CAD.