The authors assessed the association between an elevated total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio (> or = 4) and proximal coronary artery disease (CAD), as observed on multislice computed tomography. Coronary multislice computed tomographic angiography (96% on 40- or 64-slice) was performed in 295 individuals (39% women; mean age, 54 +/- 13 years) without documented CAD who were referred for coronary evaluation. Significant CAD was defined as > or = 50% stenosis in the left main, proximal left anterior descending, or > or = 2 epicardial vessels. Proximal plaque was defined as presence of any plaque in left main or proximal left anterior descending vessels. Individuals with an elevated TC/HDL-C ratio vs those without had a higher prevalence of proximal plaque (62% vs 48%, P = .04) and significant CAD (19% vs 9%, P = .009). On multivariate logistic regression analysis, only age, sex, and TC/HDL-C ratio > or = 4 were associated with significant CAD and proximal plaque.