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In times of increasing numbers of infections caused by multiresistant bacteria like MRSA (Methicillin-resistenter Staphylococcus aureus) or ESBL (Extended-Spectrum Beta-Lactamasen) producing bacteria, sufficient, but feasible cleaning and disinfection of veterinary endoscopes is of great importance. In the here described study, two cleaning- and disinfection methods (manual vs. automatized) as well as two different drying techniques (air-drying vs. pressurized air) were compared. Therefore, in 4 groups of 40 endoscopic examinations were investigated by sampling of working channel, endoscope tip and shaft at 3 time-points. Microbiologic swab results were evaluated for total bacteria numbers, successful cleaning and disinfection was defined as total bacteria of 0 or at least 4 log reduction. Overall, the percentage of successful cleaning, disinfection and drying over the different groups varied from 74 to 82%. A significant influence of the method of drying and the examined organ system was found for the working channel, while no significant factors were found for tip and shaft. Disinfection was most successful after examinations of the lower airways (P = 0.003), while odds ratios for the gastrointestinal tract and upper airways were 0.073 and 0.115, respectively. There was also a trend towards a positive effect of pressurized air drying, but this remained insignificant (P = 0.095). Overall, modern methods of disinfection and drying were found to be superior for the localizations working channel and endoscope tip (P > 0.05), but not for the shaft. In conclusion, careful cleaning and disinfection is essential in particular after endoscopic examinations of the upper airways and the gastrointestinal tract. Pressurized air drying seems preferable.