Non-invasive fractional flow reserve measured by coronary computed tomography angiography (FFRCT) has demonstrated a high diagnostic accuracy for detecting coronary artery disease (CAD) in selected patients in prior clinical trials. However, feasibility of FFRCT in unselected population have not been fully evaluated. Among 60 consecutive patients who had suspected significant CAD by coronary computed tomography angiography (CCTA) and were planned to undergo invasive coronary angiography, 48 patients were enrolled in this study comparing FFRCT with invasive fractional flow reserve (FFR) without any exclusion criteria for the quality of CCTA image. FFRCT was measured in a blinded fashion by an independent core laboratory. FFRCT value was evaluable in 43 out of 48 (89.6 %) patients with high prevalence of severe calcification in CCTA images [calcium score (CS) >400: 40 %, and CS > 1000: 19 %). Per-vessel FFRCT value showed good correlation with invasive FFR value (Spearman's rank correlation = 0.69, P < 0.001). The area under the receiver operator characteristics curve (AUC) of FFRCT was 0.87. Per-vessel accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 68.6, 92.9, 52.4, 56.5, and 91.7 %, respectively. Even in eight patients (13 vessels) with extremely severely calcified lesions (CS > 1000), per-vessel FFRCT value showed a diagnostic performance similar to that in patients with CS ≤ 1000 (Spearman's rank correlation = 0.81, P < 0.001). FFRCT could be measured in the majority of consecutive patients who had suspected significant CAD by CCTA in real clinical practice and demonstrated good diagnostic performance for detecting hemodynamically significant CAD even in patients with extremely severe calcified vessels.