Staphylococcus aureus is a frequent cause of infection in hospitalized infants. These infections are associated with increased mortality and morbidity, and longer hospital stays, but data on the burden of S. aureus disease in hospitalized infants are limited. This study compared demographics and mortality of infants with invasive methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA), determined the annual proportion of S. aureus infections that were MRSA, and compared the risk of death following an invasive MRSA infection to the risk following an invasive MSSA infection.