OBJECTIVES: Endoscopic bariatric procedures and pharmacotherapy may yield more durable weight loss than lifestyle intervention alone. Our analysis aimed to assess the cost-effectiveness of non-surgical bariatric treatments for overweight (25≤BMI<30) and mildly obese (30≤BMI<35) patients. METHODS: A state-transition model was constructed to compare three strategies: ILI, intragastric balloon (IGB), and pharmacotherapy. In the ILI strategy, patients received diet modification and behavioral therapy. In the IGB strategy, the patients faced a minor risk of gastric perforation or migration of the balloon. Side effects with IGB (e.g., nausea, vomiting, and abdominal pain) on quality of life was incorporated. In the pharmacotherapy strategy, patients received a one-year course of medication (7.5mg phentermine; 46mg topiramate). There were negligible side effects from the drug. The modeled cohort had a mean age 40 years old and 80% female, and had BMI in the overweight range (25-30) and Class I Obese range (30-35). Outcomes included costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were assessed at the end of two years. RESULTS: In mildly obese patients, pharmacotherapy led to a gain of 0.06 QALYs compared to ILI at an incremental cost of $1,094, yielding a favorable ICER of $20,083/QALY. Intragastric balloon was dominated; compared to ILI, intragastric balloon led to a gain of 0.01 QALYs and cost $4,432 more than ILI. In overweight patients, pharmacotherapy resulted in 0.02 more QALYs compared to ILI at an incremental cost of $1,094, yielding a favorable ICER of $51,261/QALY.  The IGB strategy was dominated; compared to ILI, intragastric balloon led to no change in QALYs, and cost $4,430 more than ILI. CONCLUSIONS: Pharmacotherapy may be a cost-effective weight-loss therapy for both overweight and mildly obese. Intragastric balloon may not be cost-effective because of the impact of side effects, but more robust quality-of-life data are necessary to confirm our results.