Over 17.7 million gastrointestinal (GI) endoscopic procedures are performed annually, contributing to 68% of all endoscopic procedures in the United States. Usually, endoscopic procedures are low risk, but adverse events may occur, including cardiopulmonary complications, bleeding, perforation, pancreatitis, cholangitis, and infection. Infections after the GI endoscopies most commonly result from the patient's endogenous gut flora. Although many studies have reported infection after GI endoscopic procedures, a true estimate of the incidence rate of post-endoscopy infection is lacking. In addition, the infection profile and causative organisms have evolved over time. In recent times, multi-drug-resistant microorganisms have emerged as a cause of outbreaks of endoscope-associated infections (EAI). In addition, lapses in endoscope reprocessing have been reported, with some but not all outbreaks in recent times. This systematic review summarizes the demographical, clinical, and management data of EAI events reported in the literature. A total of 117 articles were included in the systematic review, with the majority reported from North America and Western Europe. The composite infection rate was calculated to be 0.2% following GI endoscopic procedures, 0.8% following ERCP, 0.123% following non-ERCP upper GI endoscopic procedures, and 0.073% following lower GI endoscopic procedures. Pseudomonas aeruginosa was the most common culprit organism, followed by other Enterobacteriaceae groups of organisms and Gram-positive cocci. We have also elaborated different prevention methods such as antimicrobial prophylaxis, adequate sterilization methods for reprocessing endoscopes, periodic surveillance, and current evidence supporting their utilization. Finally, we discuss disposable endoscopes, which could be an alternative to reprocessing to minimize the chances of EAIs with their effects on the environmental and financial situation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)