The association of aortic regurgitation with left ventricular size, hypertrophy, and abnormal coronary flow may influence the accuracy of stress testing techniques for the diagnosis of coronary disease. We examined the diagnostic accuracy of treadmill exercise echocardiography to predict coronary artery disease in 76 patients with moderate to severe aortic regurgitation. Rest and poststress images were interpreted by 2 experienced observers, and accuracy was defined by comparison with stenoses >/=50% diameter at coronary angiography. Results were compared with accuracy in a control group of previously published studies in patients without valvular heart disease. After 6 patients were excluded because of a submaximal heart rate response (<85% age-predicted maximal heart rate), 70 patients were included in the final analysis. Patients with aortic regurgitation were of comparable age to the control group and exercised to similar workload. In 16 (23%) patients with significant coronary artery disease and significant aortic regurgitation, the sensitivity of exercise echocardiography was 56% compared with 83% in the control group (P =.03). The specificity in 54 patients with aortic regurgitation but no significant coronary artery disease was 67% compared with 83% in the control group (P =.02). Accuracy was 64% in aortic regurgitation compared with 83% in the control group (P =.02). In patients with aortic regurgitation, accuracy in the left anterior descending artery territory (76%) marginally exceeded that in the posterior (right + circumflex coronary artery) circulation (70%). Thus the presence of significant aortic regurgitation affects the regional wall motion of the left ventricle during exercise and adversely affects the accuracy of exercise echocardiography for the diagnosis of coronary artery disease.