In patients who have acute coronary syndrome (ACS), rapid and accurate risk stratification is crucial. Real-time myocardial contrast echocardiography (MCE) extends the evaluation of wall motion abnormalities by assessing myocardial perfusion. We investigated whether MCE could contribute to clinical and biochemical markers in identifying patients who have ACS when presenting to the emergency department. Consecutive patients (n = 100) who presented with first occurrence of chest pain underwent MCE to evaluate myocardial perfusion. Contrast images were also analyzed quantitatively off-line by measuring peak signal intensity (A) and slope of signal intensity increase (beta) in 16 myocardial segments. Thirty-seven of 100 patients had ACS. MCE showed perfusion defects in 9 of 12 patients (75%) who had unstable angina and had high-grade stenotic lesions on an angiogram that were missed by assessment of troponin T. MCE identified all 6 patients who had non-ST-elevation myocardial infarction and no initial increase in troponin T and 17 of 19 patients who had non-ST-elevation myocardial infarction and an initial increase in troponin T. In 2 patients who had chest pain and increased troponin T, MCE excluded ACS by identifying perimyocarditis as the underlying cause. Multivariate logistic regression analysis showed that MCE was the strongest predictor of ACS, thus adding significant diagnostic value to conventional tests. Initial perfusion defect size correlated strongly with increased troponin T at 96 hours (r = 0.73, p <0.001) and with ejection fraction at 4 weeks of follow-up (r = -0.79, p <0.001). Thus, our data suggest that MCE can accurately identify patients who have ACS.