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Abstract Background We assessed whether the non-invasive measure of peak diastolic-systolic velocity ratio (rDSVR) at rest on the left anterior descending artery (LAD) using Doppler transthoracic echocardiography is associated with obstructive coronary artery disease (CAD) on the LAD and left main (LM) arteries. We compared rDSVR diagnostic accuracy with stress wall motion (WM) and coronary flow reserve (CFR-LAD), in a group of subjects who underwent contrast stress-echocardiography (cSE) and coronary angiography within 3 months. Methods 286 patients selected with a clinical indication to cSE, in which CFR-LAD was measured during the test who also underwent coronary angiography within 3 months were selected and diagnostic performance compared. Results Demographics and clinical variables were univariate predictors of LAD or LM >50% stenosis, but rDSVR < 1.7 outperformed other variables (OR 11.18, 95% CI 5.82–21.49, p < 0.001), comprising cSE variables such as reversible WM abnormalities (OR 1.53, 95% CI 0.94–2.49, p = 0.087) or CFR-LAD < 2 (OR 2.88, 95% CI 21.74–4.77, p < 0.001). The addition of rDSVR to multivariate logistic regression models (clinical or clinical + cSE variables) led to a marked increase in C-index (0.82, 95%CI 0.78–0.87) with significant improvement compared to all prior models (p < 0.001). Conclusions Our data suggest a strict association of reduced rDSVR with >50% coronary artery stenosis on the LM/LAD, superior to other standard clinical or cSE related indexes, such as WM assessment or CFR-LAD, and builds incrementally to them and clinical variables in multivariable logistic models for the prediction of CAD on LM and LAD coronaries. Highlights • The study suggests a strict association between rest Doppler diastolic-systolic coronary flow velocity ratio (rDSVR) and coronary artery stenosis • This association is significantly higher compared with other standard clinical and also stress-echo indexes • rDSVR builds incrementally to stress-echo and clinical variables in models for the prediction of obstructive CAD on left Main and/or LAD coronary arteries [ABSTRACT FROM AUTHOR]