Trends in Staphylococcus aureus infections are not well described. To calculate incidence in overall S. aureus infection and invasive and noninvasive infections according to methicillin susceptibility and location, we conducted a 10-year population-based retrospective cohort study (1999-2008) using patient-level data in the Veterans Affairs Maryland Health Care System. We found 3,674 S. aureus infections: 2,816 (77%) were noninvasive; 2,256 (61%) were methicillin-resistant S. aureus (MRSA); 2,517 (69%) were community onset, and 1,157 (31%) were hospital onset. Sixty-one percent of noninvasive infections were skin and soft tissue infections; 1,112 (65%) of these were MRSA. Ten-year averaged incidence per 100,000 veterans was 749 (± 132 SD, range 549-954) overall, 178 (± 41 SD, range 114-259) invasive, and 571 (± 152 SD, range 364-801) noninvasive S. aureus infections. Incidence of all S. aureus infections significantly increased (p<0.001), driven by noninvasive, MRSA, and community-onset infections (p<0.001); incidence of invasive S. aureus infection significantly decreased (p<0.001).