The main aim of this study was to evaluate the clinical outcome and costs of nosocomial and community-acquired methicillin-susceptible Staphylococcus aureus (MSSA) or methicillin-resistant S. aureus (MRSA) bloodstream infection (BSI) in patients undergoing haemodialysis. A multicentre retrospective study was conducted that included 109 patients with end-stage renal disease and S. aureus BSI who were hospitalised in three German centres between 1999 and 2005. Nosocomial and community-acquired infections were analysed separately with regard to costs and outcome. Forty-nine (45%) patients had nosocomial infection. Compared to patients with community-acquired infection, these patients were more likely to have had BSI caused by MRSA (40.8% vs. 13.3%, p <0.05). BSI was the initial reason for admission for 33 (55%) patients who had community-acquired infection. The mean length of hospitalisation was 24 days for patients with community-acquired infection and 51 days for patients with nosocomial infection (p < 0.05). Costs per treatment episode were 20 024 Euros for nosocomial infection vs. 9554 Euros for community-acquired infection (p < 0.05). The average treatment costs for patients with MSSA BSI were <50% of those for patients with MRSA BSI (10 573 vs. 24 931 Euros, p <0.05). S. aureus BSI is an underlying cause of substantial health risk and high morbidity among the haemodialysis-dependent population, who are already at high-risk for other reasons. This study also highlighted differences according to the source of BSI, including costs arising from hospitalisation and treatment.