This ASGE-led multisociety guideline updates the 2016 version, to address gaps and variation in implementing infection prevention practices are common in endoscopy units across the United States. Given the rising concerns of endoscope-related infections, this guideline evaluates the current literature and standards for endoscope reprocessing and expands details related to the critical reprocessing steps of cleaning and drying and incorporates recent evidence as it pertains to improving the reprocessing of GI endoscopes.