OBJECTIVES: To estimate the nationwide annual cost for the treatment of patients hospitalized with methicillin-resistant Staphylococcus aureus (MRSA) infections in the United States. METHODS: An extensive literature search was conducted in order to identify recent studies estimating the direct medical costs associated with MRSA infections in US hospitals. The range of the annual cost of MRSA infections was constructed by multiplying the estimated number of annual discharges due to MRSA infections by the highest and lowest cost per case estimates of MRSA bacteremia and S aureus pneumonia infections. RESULTS: CDC estimated that in 2000 approximately 290,000 US patients were hospitalized with an S aureus infection and that 41.5%, or 120,000 of these were MRSA infections. The most common types of MRSA infections are skin and skin structure infections (SSSI), bacteremia, and lower respiratory tract infections. Abramson and Sexton estimated the direct medical costs associated with MRSA bacteremia to be $27,083 per case. Engemann et al. estimated the direct medical costs associated with an SSSI due to MRSA to be $28,308 per case. Rubin et al. estimated the direct medical costs associated with S aureus pneumonia to be $34,900 per case. The average cost of an MRSA-related infection, based on cited studies, ranged from $27,083 to $34,900 per case. Assuming 120,000 annual MRSA infection related hospital discharges, we estimate that the annual nationwide cost for the treatment of patients hospitalized with an MRSA infection in the US to be in the range of $3.2 billion to 4.2 billion. CONCLUSION: The annual cost for the treatment of MRSA infections incurs a significant economic burden on the US health care system. Strategies to minimize hospital costs relating to MRSA infection should be critical to the management of this economic burden placed on US hospitals.