Vancomycin is the primary antibiotic administered for treatment of methicillin-resistant S. aureus (MRSA) infection; however, treatment failure of vancomycin is currently not uncommon in patients with in vitro vancomycin susceptibile S. aureus (MIC < or = 2 microg/mL) infection. In this report, we describe a case of septic arthritis caused by persistent MRSA bacteremia and treated successfully with linezolid after failure of initial vancomycin therapy.