Details of Staphylococcus aureus bacteremia in 184 adults treated at Helsinki University Central Hospital in 1976–1979 and 1986–1989 were reviewed retrospectively, with special attention to changes in underlying factors and prognosis within the last decade. Overall mortality was 29%; it decreased from 39% in the late 1970s to 20% in the late 1980s. The independent factors associated with high mortality were rapidly fatal underlying disease, central nervous system symptoms, pneumonia, and endocarditis. There was no change in the underlying diseases between the two periods. The antibiotic treatment strategy was changed between the two periods. First, in the late 1980s the initial antibiotic was more often a penicillinase-resistant β-lactam agent and more seldom an aminoglycoside alone or in combination with a penicillinase-sensitive β-lactam. Second, combination antibiotic therapy with two efficient drugs was used more often in the late 1980s than in the late 1970s. Together these changes in antibiotic treatment strategy appear to be the most probable explanation for the improved outcome.