To identify the age- and gender-specific subpopulations of patients with acute chest pain in whom coronary computed tomographic angiography (CTA) will yield the greatest diagnostic benefit. Subjects with acute chest pain and an inconclusive initial evaluation (nondiagnostic electrocardiograhic findings, negative cardiac biomarkers) underwent contrast-enhanced 64-slice coronary CTA as a part of an observational cohort study. Independent investigators determined the presence of significant coronary stenosis (>50% luminal narrowing) and the occurrence of acute coronary syndrome (ACS) during the index hospitalization. We determined the diagnostic accuracy and effect on pretest probability of ACS using Bayes' theorem by age and gender. Of 368 patients (age 52.7 +/- 12 years, 61% men), 8% had ACS. The presence of significant coronary stenosis on CTA and the occurrence of ACS increased with age for both men and women (p <0.001). Cardiac CTA was highly sensitive and specific in women <65 years of age (sensitivity 100% and specificity >87%) and men <55 years of age (sensitivity 100% for men <45 years and 80% for men 45 to 54 years old; specificity >88.2%). Moreover, in these patients, coronary CTA led to restratification from low to high risk (for positive findings on CTA) or from low to very low risk (for negative findings on CTA). In contrast, a negative result on CTA did not result in restratification to a low-risk category in women >65 years and men >55 years old. In conclusion, the present analysis provides initial evidence that men <55 years and women <65 years might benefit more from cardiac CTA than older patients. Thus, age and gender might serve as simple criteria to appropriately select patients who would derive the greatest diagnostic benefit from coronary CTA in the setting of acute chest pain.