Aim The aim of this study was to analyze hemodynamic and clinical outcome in a cohort of 312 patients who were followed up over a period of 12 months after alcohol septal ablation (PTSMA) for symptomatic hypertrophic obstructive cardiomyopathy (HOCM). Methods and results PTSMA was intended in 337 patients with HOCM (mean age: 54 +/- 15 years), with 312 procedures completed by injection of 2.8 +/- 1.2 ml of alcohol. In 25 patients (8%) the intervention was aborted, mostly because of contrast echocardiographic findings. In the 312 patients who received alcohol, permanent pacing was necessary in 22 cases (7%); and in-hospital mortality was 1.3% (four patients). During follow-up, contact to six patients (2%) was lost, and three additional patients (1%) died. The 299 patients who either underwent non-invasive reassessment in our institution or transmitted follow-up data from their local physician formed the study population. Improvement in symptoms was reported by 272 patients (91%). Mean NYHA functional class was reduced from 2.9 +/- 0.4 to 1.5 +/- 0.7 (p < 0.0001) along with a gradient reduction (echo-Doppler) from 59 +/- 32 to 8 +/- 15 mmHg at rest, and from 120 +/- 42 to 28 +/- 32 mmHg with provocation (p < 0.0001 each). Exercise capacity improved from 94 +/- 51 to 119 +/- 40 watts (p = 0.001), and peak oxygen consumption from 18 +/- 4 to 21 +/- 6 ml/kg/min (p = 0.01). Younger age and higher outflow gradients at baseline and immediately after intervention were associated with a less favorable hemodynamic outcome. The degree of limitation of exercise capacity at baseline was the only predictor of symptomatic improvement. Conclusions Catheter-based septal ablation is an effective non-surgical technique for reducing symptoms and outflow gradients in HOCM. In contrast to a previous study, in this cohort of 312 patients there was no association between post-interventional enzyme release and hemodynamic success. Younger patients with high baseline gradients, however, tended to have a less favorable hemodynamic outcome with higher residual gradients.