Background-The purpose of this study was to compare percutaneous transluminal septal myocardial ablation (PTSMA) and septal myectomy combined with mitral leaflet extension (MLE) in symptomatic hypertrophic obstructive cardiomyopathy patients with an enlarged anterior mitral valve leaflet (AMVL). Both PTSMA and myectomy reduce septal thickness and left ventricular outflow tract (LVOT) gradient; however, an uncorrected enlarged AMVL may predispose to residual systolic anterior motion (SAM) after successful standard myectomy or PTSMA. Myectomy with MLE previously demonstrated superior hemodynamic results compared with standard myectomy, but its value relative to PTSMA is unknown. Methods and Results-Twenty-nine patients (aged 44Ϯ12 years) underwent myectomy with MLE, and 43 patients (aged 52Ϯ17 years) underwent PTSMA. Mitral leaflet area was similar in both groups (16.7Ϯ3.4 versus 15.9Ϯ2.7 cm 2 , respectively). After PTSMA, 2 patients died, 4 needed a reintervention, and 4 required a permanent pacemaker for complete heart block. After surgery, only 1 patient needed a reintervention. At 1-year follow-up, LVOT gradients did not differ between surgical and PTSMA patients (17Ϯ14 versus 23Ϯ19 mm Hg, respectively). Preinterventional mitral regurgitation grade was more severe in the surgical group, but with myectomy combined with MLE, the residual grade was similar to that of PTSMA. Mean SAM grade decreased significantly more after surgery (from 2.9Ϯ0.3 to 0.5Ϯ0.7 mm Hg versus from 2.8Ϯ0.5 to 1.3Ϯ0.9 mm Hg, PϽ0.05). Conclusions-PTSMA in these selected patients with hypertrophic obstructive cardiomyopathy had more periprocedural complications and resulted in more reinterventions. Hemodynamic results (SAM grade and reduction in mitral regurgitation) were better in surgical patients. (Circulation. 2005;112:482-488.)