Intragastric balloons (IGB) are the most widely used endoscopic bariatric and metabolic therapies. We aimed to evaluate the efficacy of IGB in comparison with sham or lifestyle interventions for weight loss in overweight and obese patients. This systematic review and meta-analysis was performed following the PRISMA guidelines. Electronic searches were performed to identify randomized controlled trials, which compared IGB with sham or lifestyle intervention. Thirteen RCTs with 1523 patients were included. The difference in mean %EWL and %TWL at follow-up was 17.98%, and 4.40%, respectively, which was significantly higher in the IGB group. Similarly, the difference in mean AWL and BMIL was 6.12 kg, and 2.13 kg/m2, respectively. IGB therapy is more effective than lifestyle intervention alone for weight loss in overweight and obese adults.