Transoral Incisionless Fundoplication (TIF) using EsophyX device is a minimally invasive endoscopic fundoplication technique. Our study aimed to assess the efficacy of TIF for atypical GERD symptoms in patients with chronic or refractory GERD.A systematic search of 4 major databases was performed. All original studies assessing atypical GERD using a validated symptom questionnaire (the Reflux Symptom Index (RSI) were included. The RSI score was assessed pre-and post-TIF at 6- and 12-month follow-up. The data on technical success rate, adverse events, proton pump inhibitor (PPI) use, and patient satisfaction were also collected. Only TIF procedures currently in practice using EsophyX device, i.e., TIF 2.0 and TIF with concomitant hiatal hernia repair (cTIF), were included in the review.A total of 10 studies (564 patients) were included. At 6- and 12- month follow-up, there was 15.72 (95% CI 12.15 to 19.29) and 14.73 points (95% CI 11.74 to 17.72) mean reduction of RSI score post-TIF, respectively, with a technical success rate of 99.5% and a pooled adverse event rate of 1%. At both time intervals, more than two-thirds of the patients were satisfied with their health condition and roughly three-fourths of the patients were off daily PPI.Our study shows that TIF using the EsophyX device is safe and effective in reducing atypical GERD symptoms at 6- and 12-month follow-up. It improves patient-centered outcomes and can be a minimally invasive therapeutic option for patients suffering from atypical GERD symptoms on chronic medical therapy.