Endoscopic resection (ER) is widely utilized as a minimally invasive treatment for upper gastrointestinal tumors; however, complications could occur during and after the procedure. Post-ER mucosal defect leads to delayed perforation and bleeding; therefore, endoscopic closure methods (endoscopic hand-suturing, the endoloop and endoclip closure method, and over-the-scope clip method) and tissue shielding methods (polyglycolic acid sheets and fibrin glue) are developed to prevent these complications. During duodenal ER, complete closure of the mucosal defect significantly reduces delayed bleeding and should be performed. An extensive mucosal defect that comprises three-quarters of the circumference in the esophagus, gastric antrum, or cardia is a significant risk factor for post-ER stricture. Steroid therapy is considered the first-line option for the prevention of esophageal stricture, but its efficacy for gastric stricture remains unclear. Methods for the prevention and management of ER-related complications in the esophagus, stomach, and duodenum differ according to the organ; therefore, endoscopists should be familiar with ways of preventing and managing organ-specific complications.