Failure in the reprocessing of thermolabile flexible endoscopes has been reported as one of the most important threats to patient health. A case report and observational study was conducted, from August 2014 to December 2019, in the Digestive Endoscopy Unit of a University Hospital in Italy, where two cases of Klebsiella pneumoniae carbapenemase ( )-producing infections in patients undergoing endoscopic retrograde cholangio-pancreatography were observed. Following the risk/safety management practices, an epidemiological investigation was started, duodenoscopes were removed from use and the reprocessing practices reviewed. Moreover, microbiological surveillance of endoscopes was carried out according to the CDC guidelines. In the first phase of sampling, 10/10 (100%) endoscopes were found to be non-compliant, of which 7 showed results for high-concern organisms (HCOs), such as - and . After implementing corrective actions, 12 out of 17 endoscopes were found to be non-compliant (70.5%), of which 8 showed results for HCOs, such as and . During the last year of regular microbiological surveillance, only 23% of endoscopes (35/152) were found to be non-compliant, of which 7 showed results for HCOs, such as and . The crucial issues were related to samples collected from the internal channels of duodenoscopes. Managing the risk associated with the reprocessing of digestive endoscopes, through risk assessment at every stage of the process, is important for the prevention of infections associated with the use of these device.