Multidetector computed tomography (MDCT) detects coronary artery disease. However, an overestimation of coronary artery stenosis and artifacts can prevent accurate identification of significant coronary narrowing. The combination of MDCT with coronary flow reserve (CFR), the hyperemic/baseline peak flow velocity ratio, measured by transthoracic Doppler echocardiography might be helpful. We studied 144 consecutive patients with CFR and quantitative coronary angiography, obtained using both MDCT and invasive coronary angiography (reference method). It was hypothesized that the CFR might provide an incremental value to MDCT in detecting significant (> or =70%) left anterior descending (LAD) coronary artery stenosis. A CFR cutoff of <2 was used to discriminate significant stenosis. CFR was feasible in 141 (98%) of 144 patients, and MDCT was feasible in 131 (91%) of 144 patients (p <0.02). In a univariate model, the prediction of significant LAD stenosis was slightly, but significantly (p <0.0001), better with CFR (sensitivity 90%, specificity 96%, positive predictive value 84%, negative predictive value 97%, and diagnostic accuracy 94%, chi-square = 97.5) than with MDCT (sensitivity 80%, specificity 93%, positive predictive value 71%, negative predictive value 95%, diagnostic accuracy 90%, chi-square = 63.2). When the findings from transthoracic Doppler echocardiography and MDCT agreed, the diagnostic accuracy increased (96%; chi-square = 86.1, p <0.0001). In a multivariate prediction of significant LAD stenosis using a logistic neural network, CFR overshadowed MDCT, and the area under the receiver operating curve was 0.99. Of the 13 patients missed by MDCT, the diagnostic accuracy of transthoracic Doppler echocardiography to predict significant LAD stenosis was 100%. Thus, CFR could improve the diagnostic accuracy of MDCT to detect significant LAD stenosis.