OBJECTIVES: Safe endoscope reprocessing requires meticulous adherence to guidelines. Human error is a principal cause of deficient reprocessing. Approaches vary from fully manual processes, to semi-automatic reprocessors, or fully automated cleaner and reprocessors. We assessed key issues in endoscope reprocessing related to guideline adherence, health and resource outcomes and staff burden. METHODS: PubMed was searched from January 1, 2007 to March 7, 2012. Search terms: ((Endoscope OR endoscopy) AND (Reprocessing OR Cleaning OR Disinfection OR Biofilms)). Abstracts were screened by 2 independent reviewers and included according to research areas: 1) adherence to endoscope reprocessing guidelines; 2) endoscopy related adverse contamination outcomes and; and 3) adverse effects of endoscope reprocessing on staff. Reference lists of key papers were searched. RESULTS: Six studies assessed guideline adherence. Non-adherence levels varied considerably with a trend for less developed healthcare systems to have poorer adherence. For study question 2, 19 articles reported 7 infection outbreaks, 6 pseudo-outbreaks and 4 toxic reactions related to endoscope procedures. The majority of events could have been prevented if standard reprocessing practices were followed. Eight studies (1 each from Canada, Japan and US and 5 from Europe) considered the impact of device reprocessing on staff health, time, or the associated costs. Two studies reported that manual reprocessing had a significant health impact on staff including respiratory ailments and physical discomfort. One study reported that in a single hospital reprocessing time was 6.2 hours longer per day with manual vs. automated procedures; this had a resultant impact on costs. CONCLUSIONS: Effective reprocessing is vital to ensure safe use of endoscopes. Guideline adherence is variable, and poor standards can lead to adverse outcomes. Manual reprocessing is associated with considerable health burdens for staff. Automated reprocessing could improve guideline adherence and reduce the burden on staff, as well as reduce costs. Further studies in this area are warranted.