We aimed to evaluate the feasibility of diagnosing coronary stenosis and myocardial ischemia with a single dual-energy CT (DECT) acquisition. Thirty-five patients underwent contrast-enhanced, ECG-gated DECT of the heart while independently operating the two tubes of a dual-source CT system at high- and low-energy X-ray spectra. From the same raw data, coronary CTA (cCTA) studies were reconstructed for stenosis detection, and the myocardial blood-pool was analyzed by determining the tissue iodine content. Two independent observers analyzed all studies for stenosis and myocardial blood-pool deficits. Results were correlated with SPECT, coronary catheterization and cCTA on a segmental basis. cCTA had 98% sensitivity, 88% specificity and 92% accuracy for detection of >50% stenosis. DECT detected myocardial ischemia with 84% sensitivity, 94% specificity and 92% accuracy. Our initial experience may warrant further exploration of DECT as a possibly feasible single imaging investigation for the comprehensive diagnosis of coronary stenosis and myocardial ischemia.