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Background: Imaging stress tests are not ideally accurate to predict anatomically obstructive CAD, leading to a non-trivial rate of unnecessary iCA. This may depend on the threshold used to indicate iCA, and maybe CTA or, one step earlier, CT calcium score could spare most unnecessary iCA in only mildly positive cSE. We assessed the diagnostic accuracy of contrast stress-echocardiography (cSE) in comparison with invasive coronary angiography (iCA), and CT angiography (CTA) only in case of equivocal tests, to find hints helping reduce falsely positive cSE in the suspicion of coronary artery disease (CAD)., Methods: Patients who were indicated cSE for suspected CAD between 2012 and 2016, who also underwent iCA were selected and diagnostic results compared. A second group, specifically with equivocal cSE who underwent CTA was also analyzed., Results: 137 subjects with equivocal cSE and CTA and 314 with cSE (any result) and iCA were selected. In the CTA-equivocal cSE group, an Agatston score < 105 and a coronary flow reserve (CFR-LAD) <1.7 had very high negative predictive value (99%, 92% respectively) to exclude obstructive CAD. The Agatston score was the most significant incremental predictor of CAD beyond clinical variables (chi square 31 to 47, p < 0.001). In the iCA group a more-than-mild reversible wall motion abnormality (WMA) demonstrated high positive predictive value for CAD (89%), while CFR-LAD appeared less useful. More-than-mild reversible WMA was the most significant predictor of CAD beyond clinical variables (chi square 37.5 to 56, p < 0.001)., Conclusions: Our data suggest iCA should be indicated only for more-than-mild reversible WMA at cSE, due to the very high positive predictive value for CAD of this finding, while mildly positive tests should be shifted to non-invasive CT, with CTA performed only for coronary calcium Agatston score > 100, since lower scores demonstrated very high negative predictive value for CAD, not justifying proceeding to CTA and even less to iCA.