This study was designed to evaluate the effect of septal reduction therapies on the conduction system for patients with hypertrophic cardiomyopathy (HCM). Heart block is a potential complication of both catheter-based and surgical procedures to relieve left ventricular outflow tract obstruction in HCM, but it is important to understand the different effects of these treatments on the conduction system. The electrocardiograms and postoperative course of patients who underwent percutaneous alcohol septal ablation or surgical myectomy at Mayo Clinic between 1999 and 2003 were reviewed. For the 58 patients who underwent alcohol septal ablation, 21 (36%) developed right bundle branch block. Six patients (12%) developed complete heart block requiring permanent pacing, three of whom had left bundle branch block before the procedure. Among the 117 patients who underwent surgical septal myectomy, 47 (40%) developed left bundle branch block. Four patients (3%) developed heart block requiring permanent pacing after the procedure, three of whom had right bundle branch block preoperatively. Percutaneous septal ablation selectively produces transmural infarction of the basal mid-septum and adjacent right bundle tissue, whereas surgical myectomy affects the endocardial portion of the basal anterior septum and adjacent left bundle tissue. These observations may help identify patients at risk for complete heart block after septal reduction procedures for HCM.