Background-Coronary lesions with a diameter narrowing ≥50% on visual computed tomographic coronary angiography (CTCA) are generally considered for referral to invasive coronary angiography. However, similar to invasive coronary angiography, visual CTCA is often inaccurate in detecting functionally significant coronary lesions. We sought to compare the diagnostic performance of quantitative CTCA with visual CTCA for the detection of functionally significant coronary lesions using fractional flow reserve (FFR) as the reference standard. Methods and Results-CTCA and FFR measurements were obtained in 99 symptomatic patients. In total, 144 coronary lesions detected on CTCA were visually graded for stenosis severity. Quantitative CTCA measurements included lesion length, minimal area diameter, % area stenosis, minimal lumen diameter, % diameter stenosis, and plaque burden [(vessel area-lumen area)/vessel area×100]. Optimal cutoff values of CTCA-derived parameters were determined, and their diagnostic accuracy for the detection of flow-limiting coronary lesions (FFR ≤0.80) was compared with visual CTCA. FFR was ≤0.80 in 54 of 144 (38%) coronary lesions. Optimal cutoff values to predict flow-limiting coronary lesion were 10 mm for lesion length, 1.8 mm2 for minimal area diameter, 73% for % area stenosis, 1.5 mm for minimal lumen diameter, 48% for % diameter stenosis, and 76% for plaque burden. No significant difference in sensitivity was found between visual CTCA and quantitative CTCA parameters (P<0.05). The specificity of visual CTCA (42%; 95% confidence interval [CI], 31%-54%) was lower than that of minimal area diameter (68%; 95% CI, 57%-77%; P=0.001), % area stenosis (76%; 95% CI, 65%-84%; P<0.001), minimal lumen diameter (67%; 95% CI, 55%-76%; P=0.001), % diameter stenosis (72%; 95% CI, 62%-80%; P<0.001), and plaque burden (63%; 95% CI, 52%-73%; P=0.004). The specificity of lesion length was comparable with that of visual CTCA. Conclusions-Quantitative CTCA improves the prediction of functionally significant coronary lesions compared with visual CTCA assessment but remains insufficient. Functional assessment is still required in lesions of moderate stenosis to accurately detect impaired FFR.