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Third space endoscopy (TSE) is a ‘magnum opus’ in the field of therapeutic gastrointestinal (GI) endoscopy that has led to a paradigm shift in the management of various GI disorders. TSE or submucosal endoscopy is based on the concept of mucosal flap safety valve technique. Since, the basic principle is more or less similar for all the TSE procedures, the nature of major adverse events (AE) also shares some similarity across the spectrum of TSE procedures. These AE include insufflation related AE, bleeding, perforation, and infection. Insufflation related events are among the most commonly encountered AEs. However, majority of the insufflation related AE do not require a specific intervention and not regarded as AE in true sense. Identification of risk factors and adaptation of preventative strategies may help in reducing the incidence of AE. At the same time, early recognition and expeditious management is paramount to reduce morbidities associated with these AE. Due to heterogeneity in the reporting of AE, it is difficult to estimate the actual incidence of AE and compare the results between different studies. Therefore, universal adaptation of a standard reporting system is required to quantify the true incidence of AE for each procedure.

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