To investigate whether exercise-induced changes of the E/E' average ratio can detect high-burden coronary artery disease (CAD) in patients with chest pain and normal left ventricular (LV) systolic function. The study population consisted of 359 patients admitted for chest pain (59.8 ± 9.8 years, 75% male). Patients underwent exercise echocardiography, scintigraphy and coronary angiography. The average of the lateral and septal ratios of early diastolic transmitral velocity to early diastolic tissue velocity (E/E') at baseline and immediately after exercise was calculated. Exercise induced wall motion abnormalities were also calculated. Coronary angiography showed flow limiting CAD in 238 patients (66%). The exercise-induced changes of E/E' average ratio had a sensitivity of 87.3% and a specificity of 75.2% for detection of flow limiting CAD, whereas myocardial scintigraphy showed 79.2% sensitivity and 80.1% specificity and exercise induced wall motion abnormalities had a sensitivity of 74.3% and a specificity of 66.9%. Likelihood ratio chi square showed an incremental value of the exercise-induced changes of E/E' average ratio over regional perfusion technique (from 121.37 to 194.15, P < 0.001) and over wall motion abnormalities (from 57.03 to 146.50, P < 0.001). The exercise-induced change of the E/E' average ratio detects flow limiting CAD in patients with chest pain and normal LV systolic function showing an incremental value over regional perfusion technique and wall motion abnormalities.