OBJECTIVE The potential for missing the diagnosis of acute myocardial infarction (AMI) and the need for appropriate use of ICU beds make early and accurate diagnostic tests to assist in this diagnosis valuable. We studied the use of serial myoglobin determinations for patients evaluated in the emergency department and admitted for possible AMI. METHODS Over a 3.5-month period, all patients presenting to the ED and admitted for suspected cardiac symptoms had serial cardiac enzymes obtained prospectively at admission and 2, 3, 4, and 6 hours after the onset of symptoms. METHODS Large urban community hospital. METHODS One hundred thirty-three consecutive patients admitted to treat or rule out AMI. RESULTS Twenty-one of 22 patients with an initially normal myoglobin that doubled within 1 to 2 hours after presentation were positive for AMI (specificity, 95%). Sensitivity of myoglobin at 2 hours after the onset of symptoms was 37% and rose to 86% at 6 hours, with 95% specificity. The negative predictive value if myoglobin was normal at 6 hours and had not doubled within 2 hours was 97% (positive predictive value, 88%). CONCLUSIONS A repeat myoglobin level that doubled within 1 to 2 hours after the initial value, even if still within the normal range, was highly specific for AMI. Serial myoglobin levels may be useful in earlier identification of AMI to help prevent inappropriate discharge from the ED and for appropriate placement in ICU beds.