BACKGROUND: Two-dimensional strain echocardiography detects early signs of left ventricular dysfunction; however, it is unknown whether myocardial strain analysis at rest in patients with suspected stable angina pectoris predicts the presence of coronary artery disease (CAD). METHODS AND RESULTS: In total, 296 consecutive patients with clinically suspected stable angina pectoris, no previous cardiac history, and normal left ventricular ejection fraction were included. All patients were examined by 2-dimensional strain echocardiography, exercise ECG, and coronary angiography. Two-dimensional strain echocardiography was performed in the 3 apical projections. Peak regional longitudinal systolic strain was measured in 18 myocardial sites and averaged to provide global longitudinal peak systolic strain. Duke score, including ST-segment depression, chest pain, and exercise capacity, was used as the outcome of the exercise test. Patients with an area stenosis≥70% in ≥1 epicardial coronary artery were categorized as having significant CAD (n=107). Global longitudinal peak systolic strain was significantly lower in patients with CAD compared with patients without (17.1±2.5% versus 18.8±2.6%; P<0.001) and remained an independent predictor of CAD after multivariable adjustment for baseline data, exercise test, and conventional echocardiography (odds ratio, 1.25 [P=0.016] per 1% decrease). Area under receiver operating characteristic curve for exercise test and global longitudinal peak systolic strain in combination was significantly higher than that for exercise test alone (0.84 versus 0.78; P=0.007). Furthermore, impaired regional longitudinal systolic strain identifies which coronary artery is stenotic. CONCLUSIONS: In patients with suspected stable angina pectoris, global longitudinal peak systolic strain assessed at rest is an independent predictor of significant CAD and significantly improves the diagnostic performance of exercise test. Furthermore, 2-dimensional strain echocardiography seems capable of identifying high-risk patients.