Background <p>Peri-and postoperative complications and recurrences are associated with the endoscopic surgical procedures for neuroendocrine tumors of the digestive system. This study aimed to evaluate the long-term outcomes and safety of endoscopic submucosal dissection and mucosal resection for neuroendocrine tumors in the digestive system.</p> Methods <p>In a retrospective cohort study, variables of minimally invasive endoscopic treatments and follow-up recurrences of 100 males and females with neuroendocrine tumors of gastric, duodenal, and rectal lesions were collected from records and analyzed. The curative resection criteria were followed the European Society of Gastrointestinal Endoscopy (ESGE) guidelines. Endoscopic ultrasound (EUS) and/or biopsy with histological assessment) routinely performed on all lesions included in this study for lesion confirmation prior to endoscopic resection.</p> Results <p>Tumor size from 6 to 11.3&#xa0;mm and endoscopic surgery procedure time from 6 to 13&#xa0;min were reported. Forty-nine, 44, and seven lesions were located in the gastric, rectal, and duodenal regions, respectively. Six (6%), 4 (4%), 16 (16%), and 5 (5%) patients reported bleeding, perforation, nausea, and vomiting, respectively, due to the surgical procedure(s). Five patients (5%) underwent recurrent endoscopic surgery. Local recurrences occurred in three (3%; two (2%) of gastric lesions and one (1%) of duodenal lesions; all grade 1) patients, and distal metastases occurred in two (2%) patients. None of the patients died during the follow-up period. Before surgery, grade 2 (<i>p</i> = 0.049), tumor size ≥ 9.5&#xa0;mm (<i>p</i> = 0.041), and gastric tract and rectal lesions (<i>p</i> = 0.021) were associated with local and/or distal metastases.</p> Conclusions <p>The prevalence of neuroendocrine tumors is high in the stomach and rectum, endoscopic resection may be safe, and high-grade tumors may be associated with a high risk of recurrence.</p>