Aims: A comparative study was conducted to evaluate the efficacy of argon plasma coagulation (APC) therapy in treating post-RYGB weight regain and the incidence of complications related to this procedure, using a sham treatment group as a control. Methods: Forty-one patients with a minimum weight regain of 10 kg and a minimum postoperative time of 36 months were randomized into two groups. Results: In the APC group (n=21), the mean initial weight was 100.4 kg and the mean weight regain was 24.94 kg. In the sham group (n=20), the mean initial weight was 103.65 kg, and the mean weight regain 25.18 kg. Anastomotic stenosis occurred only after the first APC session. The results for the comparison of APC with the sham group showed a percentage weight regain loss of 63.95 compared to -2.65, and weight loss of 15.02 and -0.57), percentage total weight loss of 14.46 and -0.62, excess weight loss of 54.32% and -2.34%), and BMI reduction of 5.38 and -0.21, with a p-value < 0.0001 for all the comparisons. In the APC group, there was a significant reduction in HbA1c (5.66% to 4.96%) and triglycerides (153.20 mg/dL to 132.20 mg/dL). Conclusion: This study indicates that APC outlet pouch reduction outperforms sham treatment in terms of weight loss for patients presenting weight regain after RYGB.