The aim of this study was to identify institution-specific risk factors for meticillin resistance in Staphylococcus aureus bloodstream infection (BSI) and to evaluate the impact of meticillin resistance on mortality. A total of 154 episodes of S. aureus BSI were identified between 1 January 2002 and 31 December 2004: 66 meticillin-resistant S. aureus (MRSA) BSI and 88 meticillin-susceptible S. aureus (MSSA) BSI. Seventy-eight episodes (51%) were considered to be community-acquired and 76 (49%) as nosocomial. Risk factors associated with MRSA BSI included not living at home (P=0.001), prior antibiotic exposure (P=0.002), insulin-requiring diabetes (P=0.028) and nosocomial BSI (P=0.031), especially more than 12.5 days after admission. There was an association between BSI-related mortality and the following variables: septic shock (P<0.001), endocarditis (P=0.002) and MRSA BSI (P=0.021). In conclusion, S. aureus BSI is a serious condition, especially when septic shock or endocarditis occurs, and is aggravated by meticillin resistance. We advise glycopeptides as empirical therapy for patients not arriving from home, those exposed to antibiotics, and those with insulin-requiring diabetes and/or nosocomial BSI.