OBJECTIVES: Individuals infected with HIV-1 are at an increased risk of Staphylococcus aureus bacteraemia (SAB). The aim of this study was to investigate mortality rate and risk of reinfection associated with SAB in HIV-1-infected individuals compared to individuals without HIV-1 infection. SETTING: University hospital treating a third of the estimated 5000 individuals with HIV infection in Denmark. PARTICIPANTS: HIV-1-infected (n=82) and sex-matched and age-matched uninfected (n=163) individuals with SAB in the time period 1 January 1995 to 31 December 2010. PRIMARY OUTCOME MEASURES: 30-day and 365-day mortality rate ratio and relative risk of reinfection. RESULTS: Individuals with HIV had an increased risk of death at day 30 (OR 11.90 (95% CI 2.15 to 65.85)) compared to individuals without HIV. Other factors associated with mortality were age, a foreign device and Pitt score. HIV-related factors did not associate to mortality. During follow-up, there were 43 episodes of reinfection; in individuals with HIV infection at an incidence rate of 7.8 (95% CI 4.7 to 10.9)/100 person-years compared with 2.2 (95% CI 1.2 to 3.2)/100 person-years for individuals without HIV. In multivariate analysis, HIV status (OR 2.91 (95% CI 1.29 to 6.58) and injection drug use (OR 3.51 (95% CI 1.06 to 11.63) were independently associated with an increased risk of reinfection. CONCLUSIONS: HIV-1 infection is associated with an increased risk of 30-day mortality after SAB and a very high rate of reinfection. Age, a foreign device and Pitt score predicted outcome. For patients infected with HIV, neither CD4 T-lymphocyte counts nor plasma HIV RNA levels were associated with 30-day outcome. TRIAL REGISTRATION NUMBER: The study was approved by the Danish Data Protection Agency (record no. 2007-41-1196).