OBJECTIVES: The objective of this study is to analyze the economic burden of exogenous endoscopy-related infections, pseudo-infections and toxic reactions in the U.S. in 2004. METHODS: The economic burden was estimated from the U.S. health care perspective. The number of events and patients involved was estimated based on a review of the literature. An analysis of the causes of contamination was conducted to evaluate preventable events. The use of resources was estimated for patients exposed, contaminated and experiencing clinical symptoms. The use of resources included chart reviews, physician visits, clinical tests, and interventions required for the treatment of the infections and toxic reactions. The valuation of resources was based on a review of the literature. A sensitivity analysis of the incidence of endoscopy-related events and the use and valuation of resources was conducted. RESULTS: The analysis yielded a baseline incidence of 2741 patients exposed to endoscopy-related events; 208 patients contaminated; and 113 patients experiencing clinical symptoms. It was estimated that 91.7% of the cases could be prevented if better infection control practices were implemented, and that 93.3% of the cases could be prevented if protective endoscope sheaths were used during procedures. The total direct medical cost associated with endoscopy-related infections occurring in the US in 2004 was estimated at $7.6 million (range = $2.8-$14.7 million). Health care expenditures for patients experiencing clinical symptoms and evaluation of patient exposed represented 61.3% and 34.8% of the total cost respectively. CONCLUSIONS: The analysis of the economic burden associated with endoscopy-related events reveals the significance of the costs related to the care of patients experiencing clinical symptoms, and the review of patients' medical charts and the clinical evaluation of exposed patients. The use of protective endoscope sheaths during procedures, improved infection control, and surveillance systems could reduce the economic burden associated with endoscopy-related events.