Echo-guided alcohol septal ablation (ASA) is an alternative treatment for highly symptomatic patients with obstructive hypertrophic cardiomyopathy (HOCM). Previous reports suggest that a low dose of alcohol (1.5-2 ml) is as effective as the classic dose (2-4 ml) used in the past. Because a larger infarct might be associated with a potential long-term risk, in this pilot study we wanted to determine whether an ultra-low dose of alcohol (1 ml) would be effective in the mid-term follow-up. Seventy patients (55+/-13 years, range 24-81 years, septum thickness <31 mm) with a highly symptomatic HOCM receiving maximum medical therapy were enrolled. Thirty-five consecutive patients (group I) have been treated with an ultra-low alcohol dose (1.0+/-0.1 ml) and compared with a control group II of 35 patients treated by the same medical team using the classic alcohol dose (2.5+/-0.8 ml) in the past. At 6-month follow-up, both groups of patients improved in dyspnea (2.9+/-0.6 vs 1.5+/-0.5 New York Heart Association [NYHA] class for group I; P<0.01, and 2.5+/-0.7 vs 1.4+/-0.4 NYHA class for group II; P<0.01) and angina (2.1+/-1 vs 0.6+/-0.8 Canadian Cardiovascular Society [CCS] class for group I; P<0.01, and 2.1+/-0.9 vs 0.7+/-0.7 CCS class for group II; P<0.01). There was a significant decrease in left ventricular (LV) ejection fraction (P<0.05), septum thickness (P<0.01), and LV outflow gradient (P<0.01) in both groups of patients. However, there was no significant difference with regard to the extent of symptomatic or echocardiographic changes and complications between both groups. These results suggest that the ultra-low dose of alcohol (1 ml) is still effective in the treatment of the majority of HOCM patients without extreme septum hypertrophy (<31 mm).