BACKGROUND AND OBJECTIVES: We hypothesized that simultaneous assessment of myocardial perfusion and a regional wall motion abnormality, using real-time myocardial contrast echocardiography (MCE), provides more useful information than routine two-dimensional echocardiography (2DE) in the diagnosis of acute coronary syndrome in patients with a non-diagnostic ECG. SUBJECTS AND METHODS: We prospectively enrolled 101 patients (age:61+/-10 years, 57 men) who presented with acute chest pain. A routine 2DE was performed to evaluate the regional wall motion abnormality, and a MCE to assess the perfusion defect. Coronary angiography was performed in all patients. The cardiac events (myocardial infarction, revascularization and death) were analyzed. RESULTS: Of the 101 patients studied, 64 had significant coronary artery disease (diameter stenosis >0%). Cardiac events occurred in 58 patients;21 myocardial infarction, 48 revascularization. The sensitivities of 2DE and MCE for significant coronary artery stenosis were 57.8 and 73.4%, and the specificities were 83.8 and 81.1%, respectively. Of the 58 patients with cardiac events, a regional wall motion abnormality was observed in 34 (59%), and a perfusion defect in 44 (76%). The specificities of 2DE and MCE for cardiac events were 79 and 77%, respectively. Cardiac events were more frequent in males, smokers and in those with an abnormal ECG (p<.05), but only a perfusion defect independently predicted cardiac events (p<.001, odds ratio=8.37). CONCLUSION: Real time MCE, in patients with acute chest pain, reasonably predicts significant coronary artery stenosis, and identifies those who will have cardiac events.