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Increasing numbers of companion animals suffering from infections with methicillin-resistant Staphylococcus aureus (MRSA) have been reported in the recent past. These infections are of particular concern because of the limited treatment options for MRSA and their transferability to humans. Since MRSA lineages isolated from infected companion animals often mirror typical human epidemic strains circulating in the same region, successful strategies to combat MRSA need strong and coordinated efforts from both, the human and the veterinary field according to the "One Health" concept. Hence, to identify potential risk factors related to MRSA infections in dogs, cats and horses, a case-control study was conducted, including data on 106 MRSA-infected animal patients as cases and 102 MSSA-infected animals as controls, originating from 155 different veterinary settings within Germany. Demographic data on animal patients, patient history and administration of antibiotics as well as practice/clinic specific parameters were assessed as putative risk factors. Multivariable logistic regression identified the following variables as risk factors for MRSA infection compared to MSSA infection: number of employees working at the veterinary setting (n>10; p<0.001), antibiotic treatment prior to sampling (systemic: p=0.002; local: p=0.049, both: p=0.011) and surgical site infection (p<0.001). Spa typing revealed predominantly clonal complexes well-known for hospital-associated lineages spreading in human health-care settings in Germany (CC5 and CC22) for isolates of dog and cat origin. CC398-MRSA dominated among equine isolates, a CC that was described as a nosocomial pathogen in equine clinical settings before. The identified risk factors and genotyping results are in accordance with numerous study outcomes from the field of human medicine and point towards reasonable problems with nosocomial spread of MRSA, especially within companion animal veterinary clinics. To define targeted infection control strategies against nosocomial pathogens, it is important to accomplish intervention studies addressing routes of transmission in companion animal veterinary settings.