Whether myocardial infarction (MI) can be diagnosed electrocardiographically in the presence of left bundle branch block (LBBB) is controversial. Our study sought to test the reliability of ECG criteria for diagnosing MI in patients with LBBB. Among 985 patients presenting within 18 hours of the onset of ischemic chest pain, 35 had complete LBBB. Acute MI was identified by serial MB-creatine kinase (CK) elevations and prior MI was determined by previously documented ECG and/or enzyme changes. Among those with LBBB, 24 patients had acute and/or prior MI, while 11 had neither. Eleven ECG criteria previously proposed for detecting MI in the presence of LBBB were evaluated. In patients presenting with ischemic chest pain and complete LBBB, presence of any one of the following ECG criteria was highly specific (90% to 100%) and predictive (85% to 100%) for acute or prior MI: Q waves in at least two of leads I, aVL, V5, or V6; R wave regression from V1 to V4; notching of the upstroke of the S wave in at least two of leads V3, V4, or V5, and primary ST-T wave changes in two or more adjacent leads.