OBJECTIVES: The objective of this study was to analyze the characteristics and costs of exogenous endoscopy-related infections, pseudo-infections, and toxic reactions in the US. METHODS: A systematic review of the scientific literature published between 1966 and 2005 was conducted in Medline. Data collection was based on a prospective protocol developed by the authors. RESULTS: The literature review included 70 outbreaks described in 64 scientific articles. Bronchoscopy accounted for half of all reported outbreaks. Inadequate decontamination practices were the leading cause of contamination; equipment malfunction became the second leading cause of contamination during the period 1990-2004. More than 91% of the infections identified could be prevented by health care providers if quality control systems are improved and implemented. The available economic information concerning exogenous endoscope related events is very limited. A model for the analysis of the economic burden of exogenous endoscopy-related events is proposed. CONCLUSIONS: Proper decontamination practices, the use of protective sheaths, and the improvement of surveillance systems could reduce the clinical and economic burdens associated with exogenous endoscopy-related events.