Background: Alcohol septal ablation (ASA) has been more commonly applied in medical refractory hypertrophic obstructive cardiomyopathy (HOCM) compared with septal myectomy (SM), however its potential to create a proarrhythmic substrate is increased. Methods: A systematic search was performed in PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to October 2020. Fixed or random effects models were used to estimate the risk ratios (RR) for ventricular arrhythmia events or other outcomes between the SM and ASA cohorts. Results: Twenty studies with 8025 patients were included. Pool analysis showed that the incidence of ventricular tachycardia (VT)/ventricular fibrillation (VF), which included appropriate implantable cardioverter defibrillator (ICD) intervention, was significantly higher in the ASA cohort than that in the SM cohort (ASA vs SM: 10% (345/3312) vs 5% (161/3227) (RR = 1.98, 95% CI (confidence interval), 1.65–2.37; p 0.00001, I{}^2 = 0%). In both groups, more than 90% of VT/VF events occurred in the early phase (during the procedure, during hospitalization or within 30 days after the procedure) (ASA: 94.20%; SM: 94.41%). Further subgroup analysis also showed that the ASA group had a higher incidence of VT/VF in both the early phase (RR = 1.94, 95% CI, 1.61–2.33; p 0.0001, I{}^2 = 0%) and the late phase (RR = 2.80, 95% CI, 1.00–7.89; p = 0.05, I{}^2 = 33%). Furthermore, although the risks of sudden cardiac death (SCD) were similar between the ASA and SM groups, a higher incidence of sudden cardiac arrest (SCA), which included SCD and resuscitated SCA, was observed in the ASA group (RR = 2.30, 95% CI, 1.35–3.94; p = 0.002, I{}^2 = 0%). Conclusions: In patients with HOCM, those who received ASA showed a higher incidence of VF/VT and SCD combined with resuscitated SCA. The majority of VT/VF occurred in the early phase.