Relief of obstruction using ventricular septal ablation (VSA) may not eliminate systolic anterior motion (SAM) of the mitral valve and mitral regurgitation (MR) in patients with obstructive hypertrophic cardiomyopathy. The hypothesis was that persistent SAM after VSA was secondary to anterior papillary muscle displacement and malcoaptation of mitral valve leaflets and that these findings could predict persistence of SAM. Echocardiograms were examined from 37 patients with obstructive hypertrophic cardiomyopathy before and 12+/-3 months after VSA. Anterior leaflet malposition (anterior-to-posterior leaflet coaptation position ratio), papillary muscle malposition (septal-to-lateral/left ventricular internal diameter ratio), and anterior position of coaptation relative to the septum (coaptation-to-septal distance) were assessed. MR proximal jet width was also measured. Of 37 patients, 30 underwent successful VSA (left ventricular outflow tract gradient reduction>50%); 22 of 30 and 7 of 7 with <50% reduction (total 29 of 37; 78%) showed persistent SAM at 12+/-3 months. These patients had more anterior malposition of the mitral valve and less MR reduction than those without SAM: anterior-to-posterior leaflet coaptation position ratio 0.42+/-0.06 versus 0.56+/-0.09, septal-to-lateral/left ventricular internal diameter ratio 0.39+/-0.12 versus 0.55+/-0.12, coaptation-to-septal distance 1.8+/-0.42 versus 2.8+/-0.30 cm, and MR reduction by 29+/-22% versus 71+/-12% (p<0.0001). Gradients, both at rest and provokable, were higher (27+/-33 vs 4+/-5 mm Hg, p=0.0004; >45 mm Hg in 9 vs 0, p=0.03, respectively) in patients with persistent SAM. Anterior malposition was present before VSA, with anterior-to-posterior leaflet coaptation position ratio<0.5 predicting SAM after VSA (p<0.0001). In conclusion, SAM and MR were often not eliminated using VSA. Mitral valve malposition was a strong predictor of SAM and MR reduction after VSA and may need to be considered in optimizing results of this procedure.