Fractional flow reserve (FFR) during invasive coronary angiography has become an established tool for guiding treatment. However, only one-third of intermediate-grade coronary artery stenosis (ICAS) are hemodynamically significant and require coronary revascularization. Additionally, the severity of stenosis visually established by coronary computed tomography angiography (CCTA) does not reliably correlate with the functional severity. Therefore, additional angiographic morphologic descriptors affecting hemodynamic significance are required. To evaluate quantitative stenosis analysis and plaque descriptors by CCTA in predicting the hemodynamic significance of ICAS and to compare it with quantitative catheter coronary angiography (QCA). QCA was performed in 65 patients (mean age 63 ± 9 years; 47 men) with 76 ICAS (40–70 %) on CCTA. Plaque descriptors were determined including circumferential extent of calcification, plaque composition, minimal lumen diameter (MLD) and area, diameter stenosis percentage (Ds %), area stenosis percentage and stenosis length on CCTA. MLD and Ds % were also analyzed on QCA. FFR was measured on 52 ICAS lesions on CCTA and QCA. The diagnostic values of the best CCTA and QCA descriptors were calculated for ICAS with FFR ≤ 0.80. Of the 76 ICAS on CCTA, 52 (68 %) had a Ds % between 40 and 70 % on QCA. Significant intertechnique correlations were found between CCTA and QCA for MLD and Ds % (p < 0.001). In 17 (33 %) of the 52 ICAS lesions on QCA, FFR values were ≤0.80. Calcification circumference extent (p = 0.50) and plaque composition assessment (p = 0.59) did not correlate with the hemodynamic significance. Best predictors for FFR ≤ 0.80 stenosis were ≤1.35 mm MLD (82 % sensitivity, 66 % specificity), and ≤2.3 mm² minimal lumen area (88 % sensitivity, 60 % specificity) on CCTA, and ≤1.1 mm MLD (59 % sensitivity, 77 % specificity) on QCA. Quantitative CCTA and QCA poorly predict hemodynamic significance of ICAS, though CCTA seems to have a better sensitivity than QCA. In this range of stenoses, additional functional evaluation is required.