The new methods for diagnosing the ischemia with coronary computed tomographic angiography (CTA) as a noninvasive test have been investigated. To compare the relative plaque volume to quantitative CTA and quantitative coronary angiography (QCA) for detecting flow-limiting coronary artery stenoses. We studied 49 patients with 55 intermediate lesions (30–69% diameter stenosis) who underwent CTA, coronary angiography (CAG), and FFR. CTA and QCA measures included lesion length, percent diameter stenosis (%DS), minimal lumen diameter (MLD), target main vessel percent plaque volume (%PV), lesion %PV, target main vessel percent lumen volume (%LV), and lesion %LV. FFR ≤0.80 was considered diagnostic of a flow-limiting lesion. The area under the receiver-operating characteristic curve (AUC) was used to determine the accuracy of detecting flow-limiting lesions. We also investigated the AUC of discrimination of flow-limiting lesion according to calcium score. Eighteen of 55 lesions (32.7%) had an FFR ≤0.80. Only vessel %PV differentiated between lesions with and without flow obstruction (67.6 vs. 62.7%, p = 0.018). The AUC for vessel %PV was greatest (0.76; 95% CI 0.61–0.87). The AUC for the discrimination of the flow-limiting lesions according to low calcium score (≤400) improved to 0.82 (95% CI 0.57–0.94). In intermediate coronary artery stenoses, vessel %PV is more accurate than conventional stenosis assessment for detecting flow-limiting lesions. In low calcium score, vessel %PV is more useful for diagnosis of ischemic heart disease compared with conventional quantitative measures.