Introduction: Colorectal cancer is a public health concern associated with high incidence rates. Sarcopenia is a known risk factor for postoperative complications, although an association between increased complications after colorectal endoscopic submucosal dissection (ESD) and sarcopenia remains undocumented. Herein, we aimed to explore the feasibility of colorectal ESD in patients with sarcopenia. Methods: This retrospective study included 499 patients (69 with and 430 without sarcopenia). We evaluated the short- and long-term outcomes of colorectal ESD. Results: There were no significant differences between the two groups regarding en bloc, R0, or curative resection rates. However, poor bowel preparation was significantly more common in the sarcopenia group. Moreover, patients with sarcopenia exhibited a significant increase in complications (37.7% vs. 10.5%). Multivariate analysis revealed that sarcopenia (odds ratio [OR]: 3.78, 95% confidence interval [Cl]: 1.85–7.73, p < 0.001), anticoagulation therapy (OR: 3.59, 95% Cl: 1.86–6.92, p < 0.001), procedure time (OR: 1.28, 95% Cl: 1.11–1.47, p < 0.001), and resection size (OR: 1.25, 95% Cl: 1.03–1.52, p = 0.02) were significantly correlated with the Common Terminology Criteria for Adverse Events (CTCAE) ≥ grade 2. The correlation between sarcopenia and CTCAE ≥ grade 2 was maintained after matching, resulting in more extended hospital stays in patients with sarcopenia. However, we detected no association between sarcopenia and overall survival and ESD-related death. Conclusion: Sarcopenia is a risk factor for complications in colorectal ESD, suggesting that colorectal ESD could be performed for patients with sarcopenia, although much caution should be taken.

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