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Background: Roux-en-Y gastric bypass (RYGB) is an effective treatment for severe obesity. However, many patients regain weight over time. The mechanisms for this are unclear, and several factors may contribute, including dilation of the gastrojejunal anastomosis. This study aimed to assess the feasibility of endoscopic gastrojejunal anastomotic tightening and to determine the effect of tightening on body weight., Methods: Eight patients with significant weight regain and dilated gastrojejunal anastomosis after RYGB were included in this pilot study. Sutures were placed endoscopically at the rim of the anastomosis. When tightened, the sutures formed tissue placations, reducing the size of the anastomotic aperture., Results: The average preprocedure body mass index (BMI) was 40.5, and the patients had regained a mean of 24 kg from their post-RYGB nadir. The average pouch length was 5.7 cm, and the average anastomotic diameter was 25 mm. The average postreduction diameter was 10.0 mm (68% reduction). Six of the eight patients showed weight loss (mean, 10 kg) at 4 months. Repeat procedures were performed for three patients who had lost 4, 5, and 9 kg, respectively with the initial procedure. After the second anastomotic reduction, the final diameters were, respectively, 14, 5, and 5 mm. The first patient did not have further weight loss. The remaining two patients showed a total weight loss of 19 and 20 kg, respectively, at 5 months. All 11 reductions were accomplished without significant complication. The average postreduction BMI was 37.7, and the percentage of excess weight loss was 23.4%., Conclusion: Peroral endoscopic suturing to tighten dilated gastrojejunal anastomoses appears technically feasible and safe. This procedure is associated with variable but significant weight loss, and preliminary results suggest that it may offer a new treatment option for postbypass weight regain in selected patients.