BACKGROUND: Both transoral incisionless fundoplication (TIF) and radiofrequency ablation (Stretta) are representative endoscopic treatments for gastroesophageal reflux disease (GERD), but they have not been directly compared. This systematic review and network meta-analysis (NMA) evaluated the comparative effects of Stretta, TIF, and proton pump inhibitors (PPIs). METHODS: PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Embase were searched for randomized controlled trials (RCTs) that compared the efficacy of either the Stretta, TIF, or PPIs/sham procedure for GERD treatment. The NMA was conducted using frequentist methods. RESULTS: A total of 516 participants from 10 RCTs were included in this NMA. Both Stretta (mean difference, MD - 9.77, 95% confidence interval, CI - 12.85 to - 6.70) and TIF (MD - 12.22, 95% CI - 15.93 to - 8.52) were significantly superior to PPIs at improving health-related quality of life (HRQL) scores and heartburn scores (Stretta: MD - 1.53, 95% CI - 2.98 to - 0.08; TIF: MD - 9.60, 95% CI - 17.79 to - 1.41). Stretta (MD - 3.77, 95% CI - 6.88 to - 0.65) was less effective at increasing lower esophageal sphincter (LES) pressure than TIF. Stretta was significantly superior to TIF (MD - 3.25, 95% CI - 5.95 to - 0.56) at improving esophageal acid exposure. Regarding the decrease in PPIs utility and esophagitis incidence, no significant differences were found between TIF and Stretta. CONCLUSION: In terms of short-term reduction of the HRQL score and heartburn score in patients with GERD, TIF and Stretta may be comparable to each other, and both may be more effective than PPIs. TIF may increase the LES pressure in comparison with Stretta and PPIs. PPIs may reduce the percentage of time pH < 4.0 when compared with TIF. This evidence should be interpreted with caution given the small number of included studies and inherent heterogeneity. Registration No. CRD42020188345.