We compared the clinical features, laboratory and coronary angiographic findings, treatments, and outcomes among patients with ST-segment elevation myocardial infarction (MI) with and without left bundle branch block (LBBB). We examined 5,742 patients with ST-segment elevation MI with and without LBBB treated with primary percutaneous coronary intervention in the Assessment of Pexelizumab in Acute Myocardial Infarction trial. The main outcome measures were obstructive coronary disease, MI, positive cardiac biomarkers, angiographic Thrombolysis In Myocardial Infarction flow, and death, MI, or congestive heart failure at 90 days. LBBB was present in 98 patients (1.7%). According to the protocol, patients with LBBB were eligible only if they had ≥1 mm concordant ST-segment elevation. Obstructive coronary artery disease was present in >87% of the patients with LBBB. Documented MI (elevated biomarkers) with an initially occluded infarct artery was more common in patients with LBBB with concordant ST-segment elevation (71.4%) than in patients without (44.1%; p = 0.027). The use of ST-segment elevation concordance criteria in the presence of LBBB was more often associated with documented MI with an identifiable culprit vessel with an initially occluded infarct-related artery. In conclusion, because a substantial proportion of patients with LBBB have acute MI with a culprit lesion and positive biomarkers, these data support immediate catheterization with the intent for primary percutaneous coronary intervention for all patients presenting with suspected ST-segment elevation myocardial infarction, ischemic symptoms, and presumed new LBBB, particularly if concordant ST-segment elevation is present.