To determine the association between serum androgens measured by high-resolution liquid chromatography-mass spectrometry and coronary artery calcium (CAC) scores. Design: Cross-sectional study. Setting: Academic institution. Patient(s): A total of 239 women, aged 40-75 years, with CAC testing and complete cardiovascular disease risk evaluation. Total T, DHEA, and androstenedione were measured using high-resolution liquid chromatography-mass spectrometry, whereas E2 and sex hormone-binding globulin were measured using commercial assays. Intervention(s): None. Main outcome measure(s): Independent associations between CAC scores and sex steroids. Result(s): Overall, 164 subjects had a CAC score < 10, 48 had a CAC score between 10 and 100, and 27 had a score > 100. There were no differences in sex hormone levels between women with CAC scores > 10 vs. CAC scores ≤ 10. In multivariable models adjusting for age, body mass index, and low-density lipoprotein cholesterol, a higher T/E2 ratio was associated with an elevated CAC score, with an unadjusted odds ratio associated with 1-SD change in log-transformed T/E2 of 1.38 (95% confidence interval 1.01-1.89) and adjusted OR 1.02 (95% confidence interval 1.002-1.04). Total T, DHEA, androstenedione, sex hormone-binding globulin, and E2 levels were not associated with increased CAC.