Alcohol-induced septal ablation (AISA) is an accepted treatment for hypertrophic cardiomyopathy (HCM) patients with left ventricular (LV) outflow obstruction who are unresponsive to medical therapy. As left atrial (LA) enlargement has been correlated with increased morbidity and mortality in HCM, we assessed LA volumes and ejection fraction (EF) prior to and after AISA using real time three-dimensional (3D) transthoracic echocardiography (TTE) in 12 patients (9 women; mean age 52 ± 15 years; 11 Caucasian). All patients underwent successful AISA with no complications and their resting left ventricular outflow gradients decreased from 40.5 ± 22.2 to 9.1 ± 17.6 mmHg (P < 0.001) while their gradients with provocation decreased from 126.2 ± 31.7 to 21.8 ± 28.0 mmHg (P < 0.001). All patients showed improvements in their New York Heart Association (NYHA) functional class. Both the LA end-systolic (45.2 ± 12.9 to 37.2 ± 13.7 ml, P < 0.0001) and end-diastolic (79.6 ± 18.9 to 77.1 ± 18.6 ml, P = 0.001) volumes decreased after AISA. The LA EF increased from 43.1 ± 9.0 to 52.5 ± 8.8% (P = 0.001). The increase in LA EF correlated with the decrease in the resting left ventricular outflow gradient (R = -0.647, P = 0.03). In conclusion, 3D echocardiography can be utilized to follow LA function after AISA for HCM. AISA results in clinical improvement in patients with HCM and in improvement of LA EF that is correlated with the decrease in the left ventricular outflow gradient. © 2008, the Authors.