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Staphylococcus aureus is a major cause of bacteremia in children and is associated with high morbidity. Complete data are lacking on the incidence, related risk factors and mortality associated with this infection.Descriptive study including patients younger than 16 years admitted to a tertiary reference hospital, with blood cultures exclusively positive for S. aureus. Four study periods were established: period 1, 1995–1999; period 2, 2000–2002; period 3, 2006–2008 and period 4, 2010–2012.In total, 269 episodes of S. aureus bacteremia (SAB) occurred in 242 patients. Over the total time studied, the incidence increased from 1.3 to 3.3 cases per 1000 patients hospitalized (relative risk: 2.71; 95% confidence interval: 1.85–3.95) and mortality decreased from 18% to 6% (P = 0.008). There were no differences in the resistance patterns of S. aureus strains. The prevalence of methicillin-resistant S. aureus (MRSA) increased from 3% to 13% between periods 1 and 2 and decreased from 14% to 3% between periods 3 and 4 (P = 0.011). The 30-day cumulative mortality was 3.3%, and the SAB-related mortality was 1.5%. Nosocomial acquisition and age 12–16 years were factors independently related with death on multivariate analysis.The incidence of SAB tripled during the years studied but remained stable in the last period. Antimicrobial resistances did not increase. Although a decrease in mortality was documented, approximately half the 30-day cumulative mortality was caused by SAB.