Our objective was to perform an updated systematic review to compare the efficacy and short- and long-term mortality of surgical myectomy (SM) and alcohol septal ablation (ASA) by including most recent and largest cohort studies published in last few years. Background: SM and ASA are the two invasive strategies used to relieve left ventricular outflow tract obstruction (LVOTO) in patients with drug refractory symptomatic hypertrophic cardiomyopathy (HCM). In the absence of a randomized trial, we tried to compare the pros and cons of the two procedures using a systematic review and meta-analysis. Method: A comprehensive search of three major databases was performed. We included original research studies comparing data on ASA and SM. Of 1,143 citations, 10 studies were included in the analysis. Results: A total of 805 patients underwent ASA and 1,019 underwent SM. Patients undergoing SM were younger (MD 6.3, P = 0.0001) and had higher reduction in the LVOT gradient (MD −9.56, P = 0.05). However, there was similar resolution of class III and IV symptoms between the two groups (P = 0.56). There was no difference in sudden cardiac death (SCD) (P = 0.93), short-term (P = 0.36), long-term all cause (P = 0.27), and long-term cardiac mortality (P = 0.58). Patients undergoing ASA had higher incidence of post procedure device implantation (OR 3.09, P < 0.00001). Conclusion: No significant difference in symptom relief was noted between the two approaches. ASA was as safe a myectomy with regards to SCD, short-term, and long-term mortality.