- The prognostic value of ST-segment depression on exercise electrocardiogram (eECG) in the setting of a normal wall motion response in a stress echocardiographic study is not well defined. The aim of the study was to compare outcomes among patients with normal wall motion during stress echocardiography with and without ischemic exercise electrocardiographic changes. A total of 4,233 patients underwent stress echocardiography from 2007 to 2010. The primary outcomes were a composite of all-cause mortality and myocardial infarction. Coronary revascularization was a secondary outcome. A Cox regression model was used for the primary analysis. Ischemic exercise electrocardiographic changes were defined as ST-segment depression of at least 1 mm, on at least 3 consecutive beats, and in at least 2 contiguous leads. A normal stress echocardiogram was present in 2,975 patients; of them, 2,228 (74%) had a normal eECG and 747 (26%) had ischemic changes on eECG. Patients with and without ischemic changes during exercise electrocardiography were similar in age and gender. At 4-years follow-up, 36 patients (2.8%) with a normal eECG experienced a primary end point versus 12 patients (1.9%) in the group with an ischemic exercise electrocardiographic response (p = 0.56). The rate of coronary revascularization was similar between the groups (7.0% and 5.7%, respectively, p = 0.2). There were no differences in the primary outcomes of patients with and without exercise electrocardiographic changes and normal stress echocardiogram (hazard ratio 1.33, 95% confidence interval 0.69 to 2.58). In conclusion, a normal wall motion response even in the setting of an ischemic exercise electrocardiographic response portends a benign prognosis in patients undergoing stress echocardiography.