Staphylococcus simulans, a coagulase-negative staphylococcus, is a common animal pathogen that is rarely encountered in human infections. We describe a 70-year-old man who developed multifocal vertebral osteomyelitis and late prosthetic joint infection caused by this pathogen. The patient was a farmer who had daily contact with cows and drank unpasteurized milk, although the portal of the pathogen's entry remains speculative. Culture of the vertebral disk biopsy specimen and cultures during resection arthroplasty yielded S. simulans. A review of the literature suggests that S. simulans may be more virulent than other species of coagulase-negative staphylococci. Accurate identification of S. simulans isolates would facilitate studies to further define its pathogenic role in human infections.