We conducted a prospective study of all cases of invasive Staphylococcus aureus infections (ISA) in the catchment area of Skaraborg Hospital (population 255,109) in western Sweden from March 2003 to February 2005. The annual incidence was 33.9 cases/100,000 population. Of these, 49% were classified as community-acquired, 32% as nosocomial and 19% as health care-associated. The mean age was 65 y. We registered children (age < or = 18 y) in 13 episodes. The most common predisposing illnesses/conditions were persons undergoing haemodialysis (relative risk 291), peritoneal dialysis (relative risk 204), persons with rheumatoid arthritis (relative risk 9), diabetes mellitus (relative risk 8), and cancer (relative risk 7). The patients were treated at various departments; only 18% of the episodes were primarily cared for at a department of infectious diseases. The most common diagnosis was soft tissue infection (27% of the episodes), bacteraemia without focus (19%), arthritis (15%), and line-associated infection (14%). A total of 197 invasive isolates was obtained, the vast majority from blood, in 141 of 170 episodes. We documented the wide spectrum of signs and symptoms. One- quarter of the patients had no history of fever, and one-third of the bacteraemia patients had normal white blood cell count (<10 x 10(9)/l) at presentation. All cases were of MSSA (methicillin-sensitive Staphylococcus aureus).