Invasive fractional flow reserve (FFR) is the gold standard for the determination of physiologic stenosis severity and the need for revascularization. FFR computed from standard acquired coronary computed tomographic angiography datasets (FFRCT) is an emerging technology which allows calculation of FFR using resting image data from coronary computed tomographic angiography (CCTA). However, the diagnostic accuracy of FFRCT in the evaluation of lesion-specific myocardial ischemia remains to be confirmed, especially in patients with intermediate coronary stenosis. We performed an integrated analysis of data from 3 prospective, international, and multicenter trials, which assessed the diagnostic performance of FFRCT using invasive FFR as a reference standard. Three studies evaluating 609 patients and 1050 vessels were included. The total calculated sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FFRCT were 82.8%, 77.7%, 60.8%, 91.6%, and 79.2%, respectively, for the per-vessel analysis, and 89.4%, 70.5%, 69.7%, 89.7%, and 78.7%, respectively, for the per-patient analysis. Compared with CCTA alone, FFRCT demonstrated significantly improved accuracy (P < 0.001) in detecting lesion-specific ischemia. In patients with intermediate coronary stenosis, FFRCT remained both highly sensitive and specific with respect to the diagnosis of ischemia. In conclusion, FFRCT appears to be a reliable noninvasive alternative to invasive FFR, as it demonstrates high accuracy in the determination of anatomy and lesion-specific ischemia, which justifies the performance of additional randomized controlled trials to evaluate both the clinical benefits and the cost-effectiveness of FFRCT-guided coronary revascularization.