BACKGROUND No large study has demonstrated that any stress test can risk-stratify future hard cardiac events (cardiac death or myocardial infarction) in patients with suspected acute coronary syndromes (ACS), nondiagnostic electrocardiographic (ECG) findings, and normal troponin levels. The aim of this study was to test the hypothesis that combined contrast wall motion and myocardial perfusion echocardiographic assessment (cMCE) during stress echocardiography can predict long-term hard cardiac events in patients with suspected ACS, nondiagnostic ECG findings, and normal troponin. METHODS A total of 545 patients referred for contrast stress echocardiography from the emergency department for suspected ACS but nondiagnostic ECG findings and normal troponin levels at 12 hours were followed up for cardiac events. Patients underwent dipyridamole-atropine echocardiography with adjunctive myocardial perfusion imaging using a commercially available ultrasound contrast medium (SonoVue). RESULTS During a median follow-up period of 12 months, 25 cardiac events (4.6%) occurred (no deaths, 12 nonfatal myocardial infarctions, 13 episodes of unstable angina). Abnormal findings on cMCE were the most significant predictor of both hard cardiac events (hazard ratio, 22.8; 95% confidence interval, 2.9-176.7) and the combined (cardiac death, myocardial infarction, or unstable angina requiring revascularization) end point (hazard ratio, 10.7; 95% confidence interval, 3.7-31.3). The inclusion of the cMCE variable significantly improved multivariate models, determining lower Akaike information criterion values and higher discrimination ability. CONCLUSIONS cMCE during contrast stress echocardiography provided independent information for predicting hard and combined cardiac events beyond that predicted by stress wall motion abnormalities in patients with suspected ACS, nondiagnostic ECG findings, and normal troponin levels.