To demonstrate that a positive CK-MB in the emergency department (ED) predicts an increased risk for complications of myocardial ischemia in patients admitted to the hospital for evaluation of chest pain.53 academic and community hospital EDs participated in this prospective observational cohort analysis of 5,120 patients with chest pain without ST-segment elevation on the initial ED 12-lead electrocardiogram. All patients were admitted for evaluation of chest pain in one of the participating hospitals as part of the National Cooperative CK-MB Project. Patients were stratified by whether or not they had an elevated CK-MB level in the ED. CK-MB measurements were made on ED presentation and two hours later. Patient medical records were reviewed for inpatient diagnoses--myocardial infarction (MI) or other diagnosis--and for ischemic complication--cardiac-related death, recurrent or delayed in-hospital MI, significant ventricular arrhythmias, new conduction defects, congestive heart failure, and cardiogenic shock.369 (7.2%) of the 5,120 patients had MI. The proportion of patients with any complication in the MI group was 24%, while the complication rate in the non-MI group was 0.4%. In all patients, regardless of final diagnosis, the relative risk of any complication was 16.1 (95% CI 11.0-23.6) in those with a positive ED CK-MB versus negative ED CK-MB patients. Similarly, the relative risk of death was 25.4 (95% CI 10.8-60.2) in positive ED CK-MB versus negative ED CK-MB patients.Multicenter data support the hypothesis that CK-MB measurements can help risk-stratify ED chest pain patients whose initial ECGs are without diagnostic ST-segment elevation.