Background- The long-term efficacy and safety of alcohol septal ablation (ASA) in patients with highly symptomatic hypertrophic obstructive cardiomyopathy has been demonstrated. The aim of this study was to evaluate the long-term outcomes of mildly symptomatic patients with hypertrophic obstructive cardiomyopathy treated with ASA. Methods and Results- We retrospectively evaluated consecutive patients enrolled in the Euro-ASA registry (1427 patients) and identified 161 patients (53±13 years; 27% women) who were mildly symptomatic (New York Heart Association [NYHA] class II) pre-ASA. The median (interquartile range) follow-up was 4.8 (1.7-8.5) years. The clinical outcome was assessed and compared with the age- and sex-matched general population. The 30-day mortality after ASA was 0.6% and the annual all-cause mortality rate was 1.7%, which was similar to the age- and sex-matched general population (P=0.62). A total of 141 (88%) patients had resting left ventricular outflow tract gradient at the last clinical checkup ≤30 mm Hg. Obstruction was reduced from 63±32 to 15±19 mm Hg (P < 0.01), and the mean NYHA class decreased from 2.0±0 to 1.3±0.1 (P < 0.01); 69%, 29%, and 2% of patients were in NYHA class I, II, and III at the last clinical checkup, respectively. Conclusions- Mildly symptomatic hypertrophic obstructive cardiomyopathy patients treated with ASA had sustained symptomatic and hemodynamic relief with a low risk of developing severe heart failure. Their survival is comparable to the general population.