Exercise stress ECG testing is not generally recommended in patients with severe aortic stenosis. Analysis of the utility of exercise testing, both with and without the use of myocardial thallium-201 scintigraphy for the diagnosis of coronary artery disease (CAD), yielded low specificity. A noninvasive, safe, and accurate diagnostic modality to ascertain the presence of CAD is not available to date for patients with severe aortic stenosis. The aim of this study was to assess the safety and diagnostic accuracy of adenosine stress echocardiography (A-Stress-Echo) and of adenosine stress myocardial perfusion scintigraphy (A-SPECT), for the detection of CAD in patients with severe aortic stenosis. The study included 50 patients with severe aortic stenosis (maximal instantaneous aortic valve gradient >80 mmHg, range 81 to 144 mmHg, and aortic valve area <0.75 cm2). All patients were submitted to A-Stress-Echo, after a 6-minute infusion of adenosine (140 microg/kg body weight/min), and then (>3 days later) A-SPECT with the same dosage of adenosine as above. Coronary angiography was performed in all patients. No major complications were observed. The unpleasant symptoms were brief and did not necessitate cessation of the test. Both modalities showed the same sensitivity (85% for A-SPECT and 85% for A-Stress-Echo) angiographically diagnosed CAD while A-Stress-Echo yielded much higher specificity (96.7% vs 76.7%). Concordance of the two methods was found in 40 cases and the specificity for those patients was 100%. A-Stress-Echo and A-SPECT, either separately or in combination, constitute excellent and safe noninvasive diagnostic methods in detecting CAD in patients with severe aortic stenosis.