<p> Endoscopic mucosal resection (EMR) is a safe and effective treatment for most large colorectal lesions Endoscopic submucosal dissection (ESD) can be performed in cases suspicious for superficial submucosal invas. This decision is often operator dependent and based on optical diagnosis of polyp morphology and surface vascular and pit pattern. Here, we conduct a systematic review and meta-analysis of ESD performed for colorectal lesions in North America to evaluate the proportion of ESD performed for benign colorectal lesions. A comprehensive literature search of multiple electronic databases was conducted to identify all studies assessing ESD for colorectal lesions in North America. The primary outcome was pooled proportion of ESD performed for benign colorectal lesions based on histopathology. Secondary outcomes included procedure-related outcomes and adverse events of ESD. Pooled proportion of ESD for benign lesions was 83.81% (95% CI: 78.8–88.2; I² 72.60%). Pooled proportion of ESD for low-grade dysplasia/sessile serrated adenomas was 52.92% (95% CI: 42.1–63.6; I² 91.10%), while pooled proportion for high-grade dysplasia was 23.34% (95% CI: 13.4–35.0; I² 93.77%). AEs were reported in 8.55% (95% CI: 5.5–12.1; I² 68.69%) of cases overall. Our meta-analysis demonstrates that a large proportion of colorectal ESD is performed for benign lesions in North America. Further studies are needed to investigate reasons contributing to the high proportion of ESD being performed for benign lesions. Our study highlights a need for standardized training pathways for optical detection, polyp selection, and endoscopic resection criteria for ESD in the North America.</p>