Objectives: Since 1998 the European Commission has funded EARSS. We present the antibiotic susceptibility results of invasive Staphylococcus aureus obtained in Spain (2000–2002).Material and methods: Forty hospitals participated in this study, covering nearly 30% of the Spanish population. All blood isolates of S. aureus were included. Laboratories used their usual methods to perform microbiological studies. Annual external quality controls were carried out. A questionnaire with hospital, patient and specimen data was completed for each isolate. Results were included in a database and analysed with WHONET 5 software.Results: Invasive S. aureus was isolated in 3113 patients. Resistance was 24.5% to oxacillin, 25.4% to ciprofloxacin, 25.2% to erythromycin and 12.1% to gentamicin. Gentamicin resistance decreased from 16.6% (2000) to 9.7% (2002). Multiresistance was observed in 68.1% of oxacillin-resistant isolates. More prevalent multiresistance profiles consisted of oxacillin–ciprofloxacin–erythromycin–gentamicin (7.4%) and oxacillin–ciprofloxacin–erythromycin (7.1%). Oxacillin resistance was significantly higher in nosocomial isolates than in those implicated in community-onset infections (26.7% versus 14.2%), in isolates from adults than in those from children (27.3% versus 4.7%), in hospitals with >500 beds than in those with <500 beds (31.1% versus 18.3%) and in isolates from Intensive Care Units than in those from other departments (39.3% versus 24%). Decreased susceptibility to vancomycin was not detected.Conclusions: In Spain, S. aureus blood isolates present a high prevalence of resistance to oxacillin, ciprofloxacin and erythromycin, as well as a high prevalence of multiresistance. Oxacillin resistance remains stable but varies in relation to hospital size, patient age, hospital department and place of infection acquisition. [ABSTRACT FROM AUTHOR]