Hospital-acquired infections with Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA) infections, are a major cause of illness and death and impose serious economic costs on patients and hospitals. However, the recent magnitude and trend of these infections have not been reported. We used national hospitalization and resistance data to estimate the annual number of hospitalizations and deaths associated with S. aureus and MRSA from 1999 through 2005. During this period, the estimated number of S. aureus-related hospitalizations increased 62%, from 294,570 to 477,927, and the estimated number of MRSA-related hospitalizations more than doubled, from 127,036 to 278,203. Our findings suggest that S. aureus and MRSA should be considered a national priority for disease control.