BACKGROUND: An important goal of noninvasive stress testing is the identification of patients with left main coronary artery or three-vessel disease, because coronary artery disease extension and severity are major prognostic factors in ischemic heart disease. Wall motion abnormalities during vasodilator stress echocardiography become apparent in more than one coronary territory only in a small number of patients with multivessel disease. The aim of this study was to assess the value of change in left ventricular ejection fraction change (ΔLVEF) to identify patients with multivessel obstructive coronary artery disease during dipyridamole stress echocardiography. METHODS: All dipyridamole stress echocardiographic studies performed at the authors' institution from October 2007 through March 2010 were retrospectively reviewed, and 150 patients who underwent coronary angiography within the next 60 days were selected. Left ventricular end-diastolic volume and end-systolic volume were measured at baseline and at the end of high-dose dipyridamole; ΔLVEF was calculated as stress ejection fraction minus rest ejection fraction. Patients were divided into four groups (controls and patients with single-vessel, two-vessel, and three-vessel disease) on the basis of coronary angiographic results. RESULTS: The mean LVEF increased significantly from rest to peak stress in all groups except the three-vessel disease group. Mean ΔLVEF was negative in patients with three-vessel or left main coronary artery disease (-2.8 ± 5.1%) and significantly lower compared with all other angiographic groups (10.2 ± 5.1% and 6.2 ± 4.1%, respectively, for single-vessel and two-vessel disease). The negative value of ΔLVEF for three-vessel disease was due mainly to increased end-systolic volume at peak stress. Receiver operating characteristic curves demonstrated excellent accuracy of ΔLVEF compared with change in wall motion score index in identifying patients with multivessel disease, with areas under the curves of 0.96 and 0.62, respectively. CONCLUSIONS: ΔLVEF is significantly lower in patients with severe coronary artery disease compared with those with single-vessel or two-vessel disease; reduced ΔLVEF identifies high-risk patients, who are likely to benefit from a more aggressive therapeutic strategy.