The presence of left bundle-branch block on the electrocardiogram may conceal the changes of acute myocardial infarction, which can delay both its recognition and treatment. We tested electrocardiographic criteria for the diagnosis of acute infarction in the presence of left bundle-branch block. The base-line electrocardiograms of patients enrolled in the GUSTO-1 (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) trial who had left bundle-branch block and acute myocardial infarction confirmed by enzyme studies were blindly compared with the electrocardiograms of control patients who had chronic coronary artery disease and left bundle-branch block. The electrocardiographic criteria for the diagnosis of infarction were then tested in an independent sample of patients presenting with acute chest pain and left bundle-branch block. Of 26,003 North American patients, 131 (0.5 percent) with acute myocardial infarction had left bundle-branch block. The three electrocardiographic criteria with independent value in the diagnosis of acute infarction in these patients were an ST-segment elevation of 1 mm or more that was concordant with (in the same direction as) the QRS complex; ST-segment depression of 1 mm or more in lead V1, V2, or V3; and ST-segment elevation of 5 mm or more that was disconcordant with (in the opposite direction from) the QRS complex. We used these three criteria in a multivariate model to develop a scoring system (0 to 10), which allowed a highly specific diagnosis of acute myocardial infarction to be made. We developed and validated a clinical prediction rule based on a set of electrocardiographic criteria for the diagnosis of acute myocardial infarction in patients with chest pain and left bundle-branch block. The use of these criteria, which are based on simple ST-segment changes, may help identify patients with acute myocardial infarction, who can then receive appropriate treatment.