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Background: Coronary angiography may not reliably predict whether a stenosis causes exercise-induced ischemia. Intracoronary Doppler ultrasound may enhance diagnostic accuracy by providing a physiological assessment of stenosis severity. The goal of this study was to compare intracoronary Doppler ultrasound with both 201Tl imaging and coronary angiography., Methods and Results: Fifty-five patients with 67 stenotic coronary arteries underwent coronary angiography with intracoronary Doppler ultrasound and had exercise 201Tl testing within a 1-week period. Coronary flow reserve was measured, and analyses were performed by independent core laboratories. The mean stenosis was 59+/-12%; 51 of 67 stenoses were intermediate in severity (40% to 70%). A coronary flow reserve < 1.7 predicted the presence of a stress 201Tl defect in 56 of 67 stenoses (agreement=84%; kappa=0.67; 95% CI=0.48 to 0.86). In the patients who achieved 75% of their predicted maximum heart rate, the Doppler and 201Tl imaging data agreed in 46 of 52 stenoses (agreement=88%; kappa=0.77; 95%CI=0.57 to 0.97). Scatter was evident when angiography was compared with coronary flow reserve (r=.43), and the angiogram did not reliably predict the results of the 201Tl stress test (kappa=0.21; agreement=57% to 63%)., Conclusions: Doppler-derived coronary flow reserve accurately predicts the presence of exercise-induced ischemia on stress 201Tl imaging, and coronary angiography does not reliably assess the physiological significance of an intermediate coronary stenosis.