We assessed gender differences in coronary plaque burden and composition amongst symptomatic patients referred for coronary computed tomographic angiography (CCTA). Over all, 916 symptomatic patients who were referred for a clinically indicated CCTA were included in the study. CCTAs were interpreted on a per-segment basis for plaque composition (non-calcified, calcified, or mixed) and stenosis severity. A stenosis of ≥50 % was considered obstructive coronary artery disease. Among 916 patients, 498 (54.3 %) patients were women. Obstructive stenosis was found in 11 % of women compared to 21 % of men (p < 0.0001). Men had significantly higher plaque prevalence, 67.9 % versus 51.6 % in women (unadjusted OR 1.98; 95 % CI, 1.51-2.60). This remained significant after adjusting for age and potential confounders (adjusted OR 2.96; 95 % CI, 2.01-4.36). A similar relationship existed for all three plaque subtypes. Men were also more likely to have mixed plaque burden (adjusted OR 1.24; 95 % CI, 1.08-1.43) than women without any significant differences in regards to the other plaque sub-types. In conclusion, symptomatic women have a lower prevalence of obstructive coronary artery disease and are less likely to have mixed coronary plaque compared to symptomatic men. Future studies are needed to determine the prognostic implications of these findings.