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Background: Endoscopic mucosal resection (EMR) is the primary treatment modality for superficial gastrointestinal mucosal lesions > 2 cm. However, the procedure carries some risk of complications including bleeding, perforation, and local recurrence. This study aimed to examine factors associated with EMR outcomes, especially in terms of local recurrence., Methods: This study retrospectively evaluated patients who underwent EMR and full closure with prophylactic clips for upper and lower gastrointestinal lesions > 2 cm at Cleveland Clinic Florida, between January 2013 and December 2018 with follow-up endoscopic evaluation for recurrence., Results: A total of 2031 endoscopic polypectomy cases were examined; 307 EMR procedures among 271 patients (52% were female, mean age 65.6 ± 11.1 years) who satisfied the inclusion criteria were included in the study. There were no perforations reported. The rate of post-polypectomy delayed bleeding was 1.6%, and the local recurrence rate in this cohort was 7.1%. Recurrent cases were successfully endoscopically managed. In the multivariate regression analysis, age > 70 years (OR = 3.20, 95% CI 1.17-8.76, p = .023), body mass index (OR = 1.12, 95% CI 1.03-1.23 p = .008), and lesion size ≥ 35 mm (OR = 11.51, 95% CI 3.54-37.40, p =  < .001) were independent predictors for recurrence., Conclusions: Age > 70 years, increased lesion size, and obesity were found to be independent predictors of local recurrence among EMR procedures for gastrointestinal lesions > 2 cm. However, there is a need for larger-scale studies on this topic., (© 2022. Springer Nature Switzerland AG.)