Staphylococcus pseudintermedius (SP) is the predominant coagulase-positive Staphylococcus isolated from canine and feline infection and carrier sites. While S. aureus is infrequent in these hosts,the emergence of MRSA in animals has renewed interest in circumstances favouring S. aureus in dogs and cats. To identify such risk factors, particularly for MRSA infection, case-control studies compared 1) S. aureus cases (MRSA and methicillin-susceptible S. aureus (MSSA)) with SP controls and 2) MRSA cases with MSSA controls. MRSA (n=99), MSSA (n=82) and SP (n=146) were isolated by a veterinary diagnostic laboratory. Confirmatory tests included demonstration of species-specific thermonuclease genes (nuc) and mecA for MRSA. SP isolates were identified as presumptive S. intermedius/SP by standard bacteriological methods; a subset was speciated biochemically as SP including tests for arginine dihydrolase, acid production from ß-gentiobiose and D-mannitol (anaerobically). MRSA carriage data of people in contact with the S. aureus-infected animals from a larger research project were included in the analysis. Data on signalment, animal health, antimicrobial therapy and veterinary interventions were collected from animal medical histories covering 6-month periods; risk factors statistically significantly associated with infection were identified by multivariable logistic regression. Use of antimicrobials and glucocorticoids doubled the risk for acquisition of S. aureus while SP infections were associated with chronicity of presenting problems and concurrent diseases. Risk factors for MRSA infection included contact with nasal carriers, post-operative wound infections and surgical implants. These findings should be considered for reviews of antimicrobial usage in veterinary medicine and of comprehensive infection control strategies for this zoonotic pathogen.