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Surgical approach (SA) is the standard treatment for infected necrotizing pancreatitis (INP) and endoscopic transgastric approach (ETA) is a promising alternative treatment. This systematic review and meta-analysis aimed to compare the effectiveness and safety of ETA versus SA in INP. Several databases were systematically searched for eligible studies that compared ETA with SA for INP. Predefined criteria were used for study selection. Three reviewers independently assessed the risk of bias. Primary outcomes included clinical resolution rate, short-term mortality, major complications, and hospital stay. Study-specific effect sizes and their 95% confidence interval (CI) were combined to calculate the pooled value using fixed-effects or random-effects model. Six studies were included with 295 patients. Major complication rate [odds ratio (OR), 0.13; 95% CI, 0.06-0.29], new-onset organ failure rate (OR, 0.26; 95% CI, 0.12-0.54), postoperative pancreatic fistula rate (OR, 0.09; 95% CI, 0.03-0.28), and incisional hernia rate (OR, 0.10; 95% CI, 0.01-0.85) were lower in the ETA group. There was a shorter hospital stay (mean difference, −17.72; 95% CI, −21.30 to −14.13) in the ETA group. No differences were found in clinical resolution, short-term mortality, postoperative bleeding, perforation of visceral organ, and endocrine or exocrine insufficiency. Compared with SA, ETA showed comparable effectiveness and safety for the treatment of INP based on current evidence.