Because alcohol septal ablation (ASA) for the treatment of symptomatic hypertrophic cardiomyopathy (HC) with left ventricular (LV) outflow tract (LVOT) obstruction results in a myocardial infarct of up to 10% of ventricular mass, LV systolic function could decline over time. We evaluated LV function during longitudinal follow-up in a cohort of patients who underwent ASA. We studied 145 consecutive patients with HC that underwent 167 ASA procedures from 2002 to 2011. Echocardiographic follow-up was available in 139 patients (96%). Echocardiographic indexes included LV ejection fraction (LVEF), mitral regurgitation severity, systolic anterior motion of the anterior mitral leaflet, and resting and provoked LVOT gradients. All patients had a baseline LVEF of >55%. LVEF was preserved in 97.1% of patients over a mean follow-up time of 3.1 ± 2.3 years (maximum 9.7). Mild LV systolic dysfunction was observed (LVEF range 44% to 54%) in only 4 patients. Mitral regurgitation severity improved in 67% (n = 112 of 138 with complete data). Resting LVOT gradient declined from a mean of 75 to 19 mm Hg (p <0.001), and provoked gradient declined from a mean of 101 to 33 mm Hg (p <0.001). New York Heart Association class improved from a mean of 2.9 ± 0.4 to 1.3 ± 0.5 (p <0.001). In conclusion, LV systolic function is only mildly reduced in a minority of patients after ASA for symptomatic HC; other echocardiographic and functional measures were significantly improved.