Objective To assess the influence of sex on the diagnostic performance of computed tomography coronary angiography (CTCA). Methods A total of 916 symptomatic patients (30.5% women) without earlier history of coronary artery intervention underwent both CTCA and invasive coronary angiography. Descriptive diagnostic parameters, to detect obstructive coronary artery disease (CAD; >= 50% lumen diameter narrowing) on CTCA, were compared between women and men on a per-patient, per-vessel, and per-segment level. Adjusted values were calculated for clustered segments and differences in sex variables using logistic multivariate regression models in general estimated equations. Results Women were older, had less typical chest complaints, and had a lower prevalence, extent, and severity of CAD compared with men. Multivariate analysis on a per-patient level revealed no difference in sensitivity (98 vs. 99%, P = 0.15), specificity (78 vs. 82%, P = 0.65), positive predictive value (PPV; 87 vs. 95%, P = 0.10), negative predictive value (NPV; 97 vs. 98%, P = 0.63), and diagnostic odds ratio (DOR; 198 vs. 721, P = 0.07). No difference was found on per-vessel level analysis (sensitivity 95 vs. 97%, P = 0.14; specificity 89 vs. 87%, P = 0.93; PPV 73 vs. 79%, P = 0.06; NPV 98 vs. 98%, P = 0.72; and DOR 143 vs. 240, P = 0.08). Per-segment analysis revealed a lower sensitivity (88 vs. 94%, P < 0.001) and DOR (163 vs. 302, P = 0.002) in women compared with men, without a difference in specificity (96 vs. 95%, P = 0.19), PPV (64 vs. 69%, P = 0.07), and NPV (99 vs. 99%, P = 0.08). Conclusion CTCA can accurately rule out obstructive CAD in both women and men. CTCA is less accurate in women to detect individual obstructive disease. Coron Artery Dis 22:421-427 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.