We present a basic mathematical model of Staphylococcus aureus transmission in the USA based on natural history of infection and nationally representative data. We employed a Susceptible-Colonized-Infected-Recovered-Susceptible compartmental modelling framework with two different phenotypes of S. aureus: methicillin-susceptible (MSSA) and methicillin-resistant (MRSA). The model is dynamic and accounts for the US population growth. For model calibration/validation, we used published 1999-2005 S. aureus infection data in conjunction with the 2001-2004 National Health and Nutrition Examination Survey colonization data. Baseline model projections illustrated how MRSA might continue to expand and gradually replace MSSA over time, in the absence of intervention, if there is strong competition for colonization. The model-based estimate of the basic reproduction number (R0) highlights the need for infection control. We illustrate the potential population-level impact of intervention with a hypothetical S. aureus vaccination component.