OBJECTIVE: To compare the risks and benefits of bypass surgery versus endovascular interventions for treating Peripheral Artery Disease (PAD). METHODS: PubMed, Google Scholar, Cochrane Library, and clinicaltrials.gov were searched until July 2023 for randomized controlled trials (RCTs) comparing bypass surgery and endovascular interventions in patients with intermittent claudication or critical limb-threatening ischemia. Primary outcomes included technical success, 30-day morbidity and mortality, one-year primary patency, and major amputation at one year. A random-effect model was employed for pooling Odds Ratios (ORs) with 95% Confidence Intervals (CIs). Subgroup and sensitivity analyses and meta-regression were used to explore heterogeneity. RESULTS: Fourteen RCTs involving 3,856 patients were included. Bypass surgery achieved significantly higher technical success (OR 8.50, 95% CI [5.46-13.25]) and one-year primary patency (OR 1.43, 95% CI [1.03-1.99]), However, it was associated with increased 30-day morbidity (OR 1.38, 95% CI [1.03-1.86]), mortality (OR 1.87, 95% CI [1.10-3.18]) and one-year major amputation rates (OR 2.58, 95% CI [1.13-5.88]) compared to endovascular interventions. Differences in one-year amputation-free survival, primary assisted and secondary patency at one year, reintervention rates within one year, 30-day MACE, post-procedural change in the ankle-brachial index, and changes in health-related quality of life at one-year, one-year clinical improvement, and one-year all-cause mortality were statistically non-significant. CONCLUSION: Endovascular interventions have a safer short-term profile but lower technical success, while bypass surgery offers better long-term patency at the cost of higher 30- day morbidity, mortality, and one-year major amputation rates. PAD treatment decisions should be tailored based on patient risk profiles and clinical goals.