Background and Aim <p>Colonic endoscopic submucosal dissection (ESD) and advanced tissue resection (ATR) in obese patients present challenges, including limited scope maneuverability, instability from abdominal fat, and slower dissection due to poor conductivity of submucosal fat. This study aims to assess the impact of obesity on colonic ESD outcomes in a large Western cohort.</p> Method <p>This retrospective study analyzed patients who underwent colonic ESD and ATR at a US tertiary institution from April 2017 to July 2024. Patients were categorized by body mass index (BMI): control (&lt; 25&#xa0;kg/m²), overweight (25 ≤ BMI &lt; 30&#xa0;kg/m²), and obese (≥ 30&#xa0;kg/m²). Multinomial logistic regression and univariate analysis were performed to evaluate the impact of weight status on clinical success, procedure time, and adverse events.</p> Results <p>A total of 637 patients were included (Control: 175, Overweight: 227, Obese: 235). En bloc resection (86.9% vs. 82.4% vs. 85.1%, <i>P</i> = 0.77) and R0 resection (78.9% vs. 72.2% vs. 74.5%, <i>P</i> = 0.16) were similar across groups. Obese patients had a significantly lower R0 resection rate for left-sided colonic lesions (<i>P</i> = 0.046). Also, obese patients more frequently required an overtube for dissection, especially for right-sided lesions (80% vs. 66%, <i>P</i> = 0.04). Procedure times were similar (<i>P</i> = 0.445), and 74.4% were safely discharged on the same day. Lack of defect closure (OR 3.072, CI 1.382–6.828) and longer procedure time (OR 1.017, CI 1.011–1.023) predicted post-procedure admission. No significant differences in adverse events were observed.</p> Conclusion <p>Obese patients had a significantly lower R0 resection rate for left-sided colonic lesions and frequently required an overtube to facilitate the dissection of right-sided colonic lesions.</p>