The purpose of this study was to evaluate the adequate cut-off value of coronary flow velocity reserve (CFVR) with transthoracic Doppler echocardiography for diagnoses of significant left anterior descending (LAD) artery stenosis in a large study population with various coronary risk factors. CFVR, which has been used for evaluation of significant coronary artery stenosis, can be reduced despite angiographically normal coronary arteries in patients with various coronary risk factors. However, the adequate cut-off value of CFVR for diagnosing significant LAD stenosis has not been fully established in patients with coronary risk factors. We examined 138 consecutive patients who underwent coronary angiography. Clinical histories of coronary risk factors were determined from interviews or medical records. CFVR assessment in the LAD artery by transthoracic Doppler echocardiography was performed in all patients. Of the 138 patients, 30 had significant stenosis, and the remainder had no stenotic lesions in the LAD artery. Receiver-operating characteristic curves for detection of significant LAD stenosis showed that a cut-off value of <2.0 was extremely precise. A cut-off value <2.0 of CFVR had a sensitivity of 90%, a specificity of 93%, a positive predictive value of 77%, and a negative predictive value of 97% for the presence of significant LAD stenosis. A cut-off value <2.0 of CFVR by transthoracic Doppler echocardiography was adequate for the diagnosis of significant LAD stenosis in a population that included patients with coronary risk factors.