Background: Coronary CT angiography (CCTA) has become an important modality to evaluate the presence of coronary artery disease. Coronary artery stenosis of intermediate severity remains a therapeutic dilemma. Measurement of fractional flow reserve (FFR) during coronary angiography is the most established technique to determine the hemodynamic severity of a coronary artery lesion. The aim of this study was to compare CCTA with FFR. Methods: In 56 coronary artery stenoses (42 patients) we performed CCTA, quantitative coronary angiography and FFR. CCTA measurements included diameter stenosis (DS, %), area stenosis (AS, %), minimal lumen diameter (MLD, mm), minimal lumen area (MLA, mm2), lesion length (LL, mm), plaque volume (mm3) and burden (%). Results: FFR averaged 0.81 ± 0.14, and 10 lesions had an abnormal FFR (< 0.75). We found significant correlations between FFR and DS (r = - 0.67, p < 0.001), AS (r = - 0.68, p < 0.001), MLD (r = 0.58, p < 0.001), MLA (r = 0.53, p < 0.001), LL (r = - 0.36, p = 0.02), plaque volume (r = - 0.36, p = 0.02) and plaque burden (r = - 0.59, p < 0.001). By multivariate regression analysis AS and LL were the strongest determinants of an abnormal FFR. The optimal cut-off value for AS was > 73% (sensitivity 90%, specificity 80%, negative predictive value 97%, and positive predictive value 50%) and for LL > 10 mm (sensitivity 60% and specificity 49%). Conclusion: This study demonstrates that quantitative CCTA is correlated to FFR. Using our CCTA criteria of abnormality, significant coronary artery stenoses can be ruled out with a high negative predictive value.