Background and Aims: Worldwide, an increasing number of duodenoscope-associated outbreaks are reported. The high prevalence rate of contaminated duodenoscopes puts patients undergoing ERCP at risk of exogenous transmission of microorganisms. The contributing factors of the duodenoscope design to contamination are not well understood. This article reports on the investigation after the outbreak of a multidrug-resistant Klebsiella pneumoniae (MRKP) related to 2 Olympus TJF-Q180V duodenoscopes. Methods: We conducted a contact patient screening and microbiologic laboratory database search. Reprocessing procedures were audited, and both duodenoscopes were fully dismantled to evaluate all potential contamination factors. Outcomes were reviewed by an experienced independent expert. Results: In total, 102 patients who had undergone an ERCP procedure from January to August 2015 were invited for screening. Cultures were available of 81 patients, yielding 27 MRKP-infected or -colonized patients. Ten patients developed an MRKP-related active infection. The 2 duodenoscopes had attack rates (the number of infected or colonized cases/number of exposed persons) of 35% (17/49) and 29% (7/24), respectively. Identical MRKP isolates were cultured from channel flushes of both duodenoscopes. The review revealed 4 major abnormalities: miscommunication about reprocessing, undetected damaged parts, inadequate repair of duodenoscope damage, and duodenoscope design abnormalities, including the forceps elevator, elevator lever, and instrumentation port sealing. Conclusions: Outbreaks are associated with a combination of factors, including duodenoscope design issues, repair issues, improper cleaning, and systemic monitoring of contamination. To eliminate future duodenoscope-associated infections, a multipronged approach is required, including clear communication by all parties involved, a reliable servicing market, stringent surveillance measures, and eventually new duodenoscope designs and reprocessing procedures with a larger margin of safety.