Methicillin-resistant Staphylococcus aureus (MRSA) has become a pathogen of animals. To compare types of infections, clinical outcomes, and risk factors associated with MRSA in dogs with those associated with methicillin-susceptible Staphylococcus aureus (MSSA) infections, we conducted a case-control study at 3 veterinary referral hospitals in the United States and Canada during 2001-2007. Risk factors analyzed were signalment, medical and surgical history, and infection site. Among 40 dogs with MRSA and 80 with MSSA infections, highest prevalence of both infections was found in skin and ears. Although most (92.3%) dogs with MRSA infections were discharged from the hospital, we found that significant risk factors for MRSA infection were receipt of antimicrobial drugs (odds ratio [OR] 3.84, p = 0.02), Beta-lactams (OR 3.58, p = 0.04), or fluoroquinolones (OR 5.34, p = 0.01), and intravenous catheterization (OR 3.72, p = 0.02). Prudent use of antimicrobial drugs in veterinary hospitals is advised.