The economic impact of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) remains unclear. We developed an economic simulation model to quantify the costs associated with CA-MRSA infection from the societal and third-party payer perspectives. A single CA-MRSA case costs third-party payers $2277-$3200 and society $7070-$20 489, depending on patient age. In the United States (US), CA-MRSA imposes an annual burden of $478 million to 2.2 billion on third-party payers and $1.4-13.8 billion on society, depending on the CA-MRSA definitions and incidences. The US jail system and Army may be experiencing annual total costs of $7-11 million ($6-10 million direct medical costs) and $15-36 million ($14-32 million direct costs), respectively. Hospitalization rates and mortality are important cost drivers. CA-MRSA confers a substantial economic burden on third-party payers and society, with CA-MRSA-attributable productivity losses being major contributors to the total societal economic burden. Although decreasing transmission and infection incidence would decrease costs, even if transmission were to continue at present levels, early identification and appropriate treatment of CA-MRSA infections before they progress could save considerable costs.