Background: Gastrointestinal leaks and fistulae are serious conditions with the potential to be life-threatening, and they are of significant relevance for both endoscopists and surgeons. These conditions may present in a wide variety of ways in clinical settings. These defects may arise from malignant or inflammatory conditions, or may be iatrogenic, occurring after surgery, endoscopic, or radiation therapy. The therapeutic approach to these conditions is often complex and is associated with a high incidence of morbidity. Consequently, in recent years, advances in interventional endoscopic techniques have earned a pivotal role in the management of gastrointestinal defects, both as a first-line treatment and as a rescue therapy. The advent of clips and luminal stents marked the advent of gastrointestinal defect therapy. However, the advent of innovative endoscopic closure devices and techniques, such as endoscopic internal drainage, suturing systems, and vacuum therapy, has broadened the indications of endoscopy for the management of gastrointestinal wall defects. This is because surgical therapy still tends to be complex and is plagued by high rates of morbidity. Summary: A successful endoscopic management of gastrointestinal leaks and fistulae necessitates a tailored and multidisciplinary approach, based on the aforementioned factors, in addition to local expertise and the availability of devices. Moreover, a standardized evidence-based algorithm for the management of GI defects is still not available. Endotherapy represents a minimally invasive, effective approach with lower morbidity and mortality compared to surgical techniques.

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