Persistent nasal carriers and noncarriers of Staphylococcus aureus were inoculated with a mixture of different S. aureus strains. The majority of noncarriers and nearly all persistent carriers returned to their original carrier state after artificial inoculation. Furthermore, the majority of persistent carriers tested positive again for their original resident strain. Using a human nasal inoculation model, we here demonstrate that the human factor is an important determinant of S. aureus nasal carriage.