Abstract Angiographically assessed plaque morphology, not only plaque severity, may affect myocardial vulnerability to ischemia during stress testing. The aim of this study was to evaluate directly, in a head-to-head comparison, the relation between coronary stenosis severity and morphology and pharmacologic stress echo response. From our inpatients echo databank, we selected 68 patients (62 men, mean age 57 ± 9 years) who had undergone high-dose dipyridamole and high-dose dobutamine-atropine echocardiography, performed within 1 week and in random order, before coronary angiography that showed significant coronary artery disease by selection. There were altogether 121 vessels with visually assessed stenosis >50% in 68 patients. Thirty-three had complex-type and 56 simple-type lesions (according to the Ambrose classification), whereas 32 vessels were occluded. During dobutamine echocardiography there were 51 dyssynergic regions of the left ventricle fed by different coronary arteries in 50 patients and dipyridamole stress was able to induce ischemia in 45 separate regions in 44 patients. The overall agreement between the 2 tests in recognizing ischemia was 76%. Induced ischemia was associated with greater quantitatively assessed stenosis severity for both dipyridamole (positive, 70 ± 12% vs negative, 63 ± 12% area reduction; p <0.05) and dobutamine (positive, 68 ± 12% vs negative, 63 ± 12% area reduction; p <0.05). The simple-type stenosis was more frequently identified with dobutamine (46%) versus dipyridamole (21%, [p <0.01]), whereas the complex-type stenosis was associated with a trend toward more frequent positivity of dipyridamole (55%) versus dobutamine (36%), p = 0.13. Adenosinergic stress positivity is affected not only by plaque severity, but also by plaque morphology, whereas adrenergic stress positivity is affected by plaque severity, not by plaque morphology.