Background: Longitudinal 2D strain of left ventricle (LV) might reveal subtle changes from myocardial ischemia. We sought to know whether peak systolic longitudinal strain (PSLS) by 2D strain method could predict the presence of significant coronary artery disease (CAD) even in the patients with normal resting wall motion. Methods: Consecutive 349 patients who underwent exercise stress echocardiography (ESE) and coronary evaluation with coronary angiography (CAG) and/or multi-detector computed tomography (MDCT) were evaluated. Exclusion criteria were as follows; patients with previous cardiac surgery, abnormal resting wall motion, cardiomyopathy, valvular heart disease, variant angina and atrial fibrillation. In the case of significant or equivocal MDCT results, CAG was performed. Otherwise, the cases were also excluded. Patients were grouped according to the coronary evaluation as CAD group versus normal. From the resting image of ESE, the global and segmental PSLS of basal, mid and apical LV were analyzed offline. Results: After excluding patients with above criteria, 193 patients were eligible for analysis. PSLS of every segment of LV could be obtained successfully with good tracking quality in 82% (159/193) patients. Global LV PSLS was significantly lower in CAD group than in normal group (-19.6% 짹 2.0% versus -21.8% 짹 2.1%, p<0.001). Receiver operational characteristic curve demonstrated that global PSLS could predict CAD group with cutoff value of -21.2% (sensitivity 78%, specificity 71% and area under curve=0.79, 95%CI=0.72-0.86). Segmental analysis showed that mid LV PSLS could predict CAD most efficiently with cutoff value of -19.3% (sensitivity 61% and specificity 83% and area under curve=0.77, 95%CI=0.69-0.84). ESE could predict CAD group with sensitivity of 81% (62/77) and specificity of 82% (67/82). In multivariable logistic analysis, reduced PSLS (cutoff value of -21.2%) could predict significant CAD (OR=4.6, 95%CI 1.77-11.7, p=0.002) independently with ESE results (OR=12.1, 95%CI, 5.05-29.0, p<0.001). Conclusions: Reduced LV PSLS at rest even in the patients with normal wall motion might be an independent predictor for the significant CAD.