Background The impact of ethanol dose on the long-term outcome of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy was investigated. Methods and Results Fifty-four patients (age 24-82 years; 65% women) undergoing ASA were randomized into 2 groups according to the dose of injected ethanol: Group A 1-2 ml, Group B >2 ml. Clinical and echocardiographic data were obtained at baseline and during follow-up. The volume of ethanol injected was 1.50±0.4 and 2.60±0.6 ml (p<0.001) with a subsequent peak of creatine kinase-MB of 2.25±1.00 and 2.62±1.57 μkat/L (p=0.02) in Groups A and B, respectively. The median follow-up was 39 (range 6-72) months after ASA, during which 1 patient died and 1 repeat procedure was necessary in both groups of patients. Both groups had a significant and similar improvement in outflow pressure gradient, dyspnea (New York Heart Association functional class) and angina pectoris (Canadian Cardiovascular Society class) (p<0.001). There was a significant decrease in the left ventricular ejection fraction (LVEF) in Group B (81±7 vs 75±7%; p=0.002), but not in Group A (80±7 vs 79±7%; p=0.67). Thinning of the basal septum was more pronounced in Group B than in Group A (9.3±5.7 vs 6.6±3.4 mm; p=0.04). Conclusions A lower dose of ethanol injected into the target septal branch reduces both the size of necrosis and subsequent thinning of the basal septum, and preserves LVEF during long-term follow-up. Moreover, the low dose (1-2 ml) is as safe and as hemodynamically efficacious as higher doses. (Circ J 2006; 70: 1550 - 1552)