BACKGROUND: It remains unclear whether myocardial contrast echocardiography (MCE) is as accurate as myocardial perfusion imaging with technetium-99m sestamibi (MPI) for the diagnosis of acute coronary syndrome (ACS). We sought to directly compare the diagnostic accuracy of MCE with resting MPI in a head-to-head fashion. METHODS: We prospectively enrolled 98 consecutive patients (mean age; 59+/-9 years, 68 males) who presented to the emergency department with chest pain suggestive of acute myocardial ischemia. Early MCE was performed by using continuous infusion of perfluorocarbon-exposed sonicated dextrose albumin (PESDA) during intermittent power Doppler harmonic imaging. Myocardial perfusion defects observed in at least one coronary territory were considered positive. Sestamibi was injected immediately after MCE and MPI was obtained within 6 hours of tracer injection. RESULTS: ACS was confirmed in 67 patients. There were 32 patients with acute myocardial infarction (AMI) and 35 patients with unstable angina requiring urgent revascularization. The sensitivities of MCE and MPI for the diagnosis of ACS were 72% and 61%, respectively, which were significantly higher than those of ST segment change (24%, p<0.001 vs. MCE and vs. MPI) and troponin I (27%, p<0.001 vs. MCE and vs. MPI), with similar specificities of 90% to 100%. On a receiveroperating characteristics curve demonstrating diagnostic accuracy for ACS, the area under the curve of MCE was significantly larger than that of MPI (0.86 vs. 0.77, respectively; p=0.019). CONCLUSION: MCE and MPI overcome the low sensitivity of routine triage tests for detecting ACS, and MCE is more accurate than MPI for the diagnosis of ACS in the emergency department.