Myoglobin is an early marker of cardiac injury, although positive results occur in the absence of cardiac myonecrosis. We studied data for 537 patients admitted to the emergency department with symptoms suggestive of myocardial injury who underwent testing for troponin I (TnI), creatine kinase isoenzyme (CK-MB), and myoglobin at the point of care. Physicians were blinded to the myoglobin results. Myoglobin had a sensitivity of 69.7% and a negative predictive value of 97.4% for the diagnosis of acute coronary syndrome (ACS) on "first-draw" specimens. Receiver operating characteristic curve analysis suggested that myoglobin demonstrated optimal sensitivity for ACS, while TnI had optimal specificity. CK-MB was neither the most specific nor the most sensitive marker. More than 80% of the patients with false-positive myoglobin results were admitted to the hospital. These data invalidate concerns regarding the putative overtreatment effect of false-positive cases owing to myoglobin results. Furthermore, our data suggest that myoglobin is superior to CK-MB as an adjunct to TnI.