The presence of bundle branch block (BBB) has been associated with poor outcomes in patients who have acute myocardial infarction. Whether this is true in the angioplasty era is not known. We sought to evaluate the outcome of patients with acute myocardial infarction and BBB who were treated with primary angioplasty. We evaluated 3,053 patients who underwent emergency catheterization in the PAMI trials. Patients who had left BBB (n = 48, 1.6%) on presenting electrocardiogram were compared with patients who had right BBB (n = 95, 3.1%) or no BBB (n = 2,910, 95.3%). Patients who had BBB were older and more frequently had diabetes mellitus, peripheral vascular disease, and previous coronary artery bypass grafting. They had lower ejection fraction and more multivessel disease. There were no significant differences in door-to-balloon time, final Thrombolysis In Myocardial Infarction flow grade or stent use. In-hospital major adverse cardiac events (death, ischemic target vessel revascularization, and reinfarction) were higher in patients who had BBB due primarily to increased in-hospital death (left BBB 14.6%, right BBB 7.4%, no BBB 2.8%, p < 0.0001). In multivariate logistic regression analysis, left BBB was an independent predictor of in-hospital death (odds ratio 5.53, 95% confidence interval 1.89 to 16.1, p = 0.002). In conclusion, patients who have acute myocardial infarction and BBB have increased co-morbidities and higher mortality rates despite treatment with primary angioplasty. Despite early identification of multivessel disease with triage to angioplasty or coronary artery bypass grafting, if necessary, similar treatment times, and final Thrombolysis In Myocardial Infarction grade 3 flow, the presence of left BBB on admission electrocardiogram in patients who have acute myocardial infarction is an independent predictor of in-hospital mortality. Because 85% of deaths in patients who have left BBB occur within the first week, these patients should be recognized early and receive prompt and aggressive treatment.