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In the past, the treatment of iatrogenic gastrointestinal perforations was limited to surgical management or to medical observation. Natural Orifice Transluminal Endoscopic Surgery (NOTES) has paved the way towards the development of reliable endoscopic closure techniques, which can be applicable in accidental perforations of the gastrointestinal tract. When endoscopic treatment is feasible, hemoclips are preferred in smaller perforations, while over-the-scope-clips or a combination of hemoclips, endoloops, and glue are used in larger ones. Endoscopic stitching is rarely utilized, and endoscopic stapling has been practically abandoned. The use of self-expandable covered stents can be considered in the esophagus and duodenum. Broad spectrum antibiotics are recommended in most cases. Clinical follow-up in a medico-surgical unit is mandatory and surgical intervention should not be delayed more than 24h if clinical or biological worsening occurs. Imaging with oral contrast medium is advisable before resumption of oral feeding in the case of large perforations.