The implications of an elevated Creatine kinase (CK)-MB isoenzyme (MB) in suspected acute coronary syndromes, with a normal total CK, is not well established. Despite many guidelines on managing patients with acute coronary ischemia, none indicates strategies for patients with elevated MB and with a normal CK. The outcome consequence of this result is not firmly established. Our objective was to prospectively evaluate outcomes in patients with suspected acute coronary syndromes, normal initial total CK, and increased MB. All Emergency Department patients with suspected acute coronary syndromes and creatinine < 2.0 mg/dL were eligible for study entry. Serial CK and MB fractions were measured on arrival in the Emergency Department, then 8 and 16 h postpresentation. A composite outcome of death, Q-wave myocardial infarction, or revascularization was defined at the index visit and 6 months later. Outcomes were determined by blinded record review and by telephone contact. In the 698 patients entered, the acute composite outcome rate was 25% (175) and 6.3% (44) at 6 months. Acute and 6 month adverse outcome rates were statistically the same for all patients with an elevated MB fraction, regardless of the total CK level. An elevated MB conferred a higher event rate than did a normal MB. We conclude that the adverse event rate for patients with suspected acute coronary syndromes and an elevated MB is the same whether or not the total CK is elevated. These patients should be considered as having had an acute coronary syndrome.