Alcohol septal ablation (ASA) has been proven to reverse left ventricular (LV) remodeling in hypertrophic cardiomyopathy (HCM). However, there are no studies on the effect of sex on LV remodeling after ASA. We aimed to investigate whether sex differences affect the process of LV remodeling and outcome after ASA. A total of 107 patients with obstructive HCM (54 men and 53 women, mean age 51 ± 8 years) were recruited. Cardiovascular magnetic resonance (CMR) was performed at baseline and 16 months after ASA. The extent of late gadolinium enhancement (LGE) was measured. Women had a higher indexed LV mass and smaller indexed LV end-systolic volumes than men at the time of ASA. After ASA, both men and women exhibited a regression of LV mass, and the percentage of mass regression was greater in men than women (15.3% ± 4.3% vs. 10.7% ± 1.8%, p < 0.001). In multivariable analysis, male sex, higher reduction of LV outflow tract (LVOT) gradient and lower baseline LV mass index were independently associated with greater LV mass regression after ASA. Kaplan-Meier analysis showed significantly higher cardiovascular events in women than in men (p = 0.015). Female sex [hazard ratio (HR) 3.913, p = 0.038] and LV mass preablation (HR, 1.019, p = 0.010) were independent predictors of cardiovascular outcomes. Males with HCM had favorable reverse remodeling with greater LV mass regression post-ASA than female patients. This favorable LV reverse remodeling might provide a mechanistic explanation for the survival advantage in men.