Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly a cause of nosocomial and community-onset infection with unknown national scope and magnitude. We used the National Hospital Discharge Survey to calculate the number of US hospital discharges listing S. aureus-specific diagnoses, defined as those having at least 1 International Classification of Diseases (ICD)-9 code specific for S. aureus infection. The number of hospital discharges listing S. aureus-specific diagnoses was multiplied by the proportion of methicillin resistance for each corresponding infection site to determine the number of MRSA infections. From 1999 to 2000, an estimated 125,969 hospitalizations with a diagnosis of MRSA infection occurred annually, including 31,440 for septicemia, 29,823 for pneumonia, and 64,706 for other infections, accounting for 3.95 per 1,000 hospital discharges. The method used in our analysis may provide a simple way to assess trends of the magnitude of MRSA infection nationally.