BEST PRACTICE ADVICE 1: For all procedures, especially procedures carrying an increased risk for perforation, a thorough discussion between the endoscopist and the patient (preferably together with the patient's family) should include details of the procedural techniques and risks involved. BEST PRACTICE ADVICE 2: The area of perforation should be kept clean to prevent any spillage of gastrointestinal contents into the perforation by aspirating liquids and, if necessary, changing the patient position to bring the perforation into a non-dependent location while minimizing insufflation of carbon dioxide to avoid compartment syndrome. BEST PRACTICE ADVICE 3: Use of carbon dioxide for insufflation is encouraged for all endoscopic procedures, especially any endoscopic procedure with increased risk of perforation. If available, carbon dioxide should be used for all endoscopic procedures. BEST PRACTICE ADVICE 4: All endoscopists should be aware of the procedures that carry an increased risk for perforation such as any dilation, foreign body removal, any per oral endoscopic myotomy (Zenker's, esophageal, pyloric), stricture incision, thermal coagulation for hemostasis or tumor ablation, percutaneous endoscopic gastrostomy, ampullectomy, endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), endoluminal stenting with self-expanding metal stent (SEMS), full-thickness endoscopic resection, endoscopic retrograde cholangiopancreatography (ERCP) in surgically altered anatomy, endoscopic ultrasound (EUS)-guided biliary and pancreatic access, EUS-guided cystogastrostomy, and endoscopic gastroenterostomy using a lumen apposing metal stent (LAMS). BEST PRACTICE ADVICE 5: Urgent surgical consultation should be highly considered in all cases with perforation even when endoscopic repair is technically successful. BEST PRACTICE ADVICE 6: For all upper gastrointestinal perforations, the patient should be considered to be admitted for observation, receive intravenous fluids, be kept nothing by mouth, receive broad-spectrum antibiotics (to cover Gram-negative and anaerobic organisms), nasogastric tube (NGT) placement (albeit some exceptions), and surgical consultation. BEST PRACTICE ADVICE 7: For upper gastrointestinal tract perforations, a water-soluble upper gastrointestinal series should be considered to confirm the absence of continuing leak at the perforation site before initiating a clear liquid diet. BEST PRACTICE ADVICE 8: Endoscopic closure of esophageal perforations should be pursued when feasible, utilizing through-the-scope clips (TTSCs) or over-the-scope clips (OTSCs) for perforations2 cm and endoscopic suturing for perforations2 cm, reserving esophageal stenting with SEMS for cases where primary closure is not possible. BEST PRACTICE ADVICE 9: Endoscopic closure of gastric perforations should be pursued when feasible, utilizing TTSCs or OTSCs for perforations2 cm and endoscopic suturing or combination of TTSCs and endoloop for perforations2 cm. BEST PRACTICE ADVICE 10: For large type 1 duodenal perforations (lateral duodenal wall tear3 cm), being cognizant of the difficulty in closing them endoscopically, urgent surgical consultation should be made while the feasibility of endoscopic closure is assessed. BEST PRACTICE ADVICE 11: Because type 2 periampullary (retroperitoneal) perforations are subtle and can be easily missed, the endoscopist should carefully assess the gas pattern on fluoroscopy to avoid delays in treatment and request a computed tomography scan if there is a concern for such a perforation; identified perforations of this type at the time of ERCP may be closed with TTSCs if feasible and/or by placing a fully covered SEMS into the bile duct across the ampulla. BEST PRACTICE ADVICE 12: For the management of large duodenal polyps, endoscopic mucosal resection (EMR) should only be performed by experienced endoscopists and endoscopic submucosal dissection (ESD) only by experts because both EMR and ESD in the duodenum require proficiency in resection and mucosal defect closure techniques to manage immediate and/or delayed perforations (caused by the proteolytic enzymes of the pancreas). BEST PRACTICE ADVICE 13: Endoscopists should be aware that colon perforations occurring during diagnostic colonoscopy are most commonly located in the sigmoid colon due to direct trauma from forceful advancement of the colonoscope. Such tears recognized at the time of colonoscopy may be closed by TTSCs or OTSCs if the bowel preparation is good and the patient is stable. BEST PRACTICE ADVICE 14: Although colon perforation is responsive to various endoscopic tools such as TTSC, OTSC, and endoscopic suturing, perforations in the right colon, especially in the cecum, have been relegated to using only TTSCs because of inability to reach the site of the perforation with an endoscopic suturing device or OTSC if the colon is tortuous or unclean. Recently a new suture-based device for defect closure has been introduced allowing deep submucosal and intramuscular enhanced fixation through a standard gastroscope or colonoscope. BEST PRACTICE ADVICE 15: Patients with perforations who are hemodynamically unstable or who have suffered a delayed perforation with peritoneal signs or frank peritonitis should be surgically managed without any attempt at endoscopic closure. BEST PRACTICE ADVICE 16: In any adverse event including perforation, it is paramount to ensure accurate documentation, prompt discussion with the patient and family, and swift reporting to the quality officer (or equivalent) and risk management team of the institution (in major adverse events).