OBJECTIVES: This study sought to test the hypothesis that right bundle branch block (RBBB) patients have larger scar size than left bundle branch block (LBBB) patients do. BACKGROUND: A proximal septal perforating branch of the left anterior descending (LAD) coronary artery most commonly perfuses the right bundle branch and left anterior fascicle, but not the left posterior fascicle. Thus, proximal LAD occlusions should cause RBBB, not LBBB. METHODS: We performed electrocardiograms and magnetic resonance imaging for scar quantification in 233 patients with left ventricular (LV) ejection fraction ≤35% who were receiving primary prevention implantable cardioverter-defibrillators (ICD cohort). Scar size and location were compared among patients with RBBB, LBBB, nonspecific LV conduction delay, and QRS <120 ms. A second cohort of 20 hypertrophic cardiomyopathy patients undergoing alcohol septal ablation was studied to determine whether controlled infarction in a proximal LAD septal perforator caused RBBB or LBBB. RESULTS: In the ICD cohort, LV ejection fraction was similar between RBBB and LBBB patients (24.9% vs. 25.0%; p = 0.98); however, RBBB patients had significantly larger scar size (24.0% vs. 6.5%; p < 0.0001). Patients with nonspecific LV conduction delay or QRS <120 ms had intermediate scar size (12.9% and 14.4%, respectively). Those with RBBB (compared with LBBB) were more likely to have ischemic heart disease (79% vs. 29%; p < 0.0001). In the alcohol septal ablation cohort, 15 of 20 patients (75%) developed RBBB, but no patients developed LBBB. CONCLUSIONS: In patients with LV ejection fraction ≤35%, RBBB is associated with significantly larger scar size than LBBB is, and occlusion of a proximal LAD septal perforator causes RBBB. In contrast, LBBB is most commonly caused by nonischemic pathologies.