IMPORTANCE Staphylococcus aureus bacteremia (SAB) in children causes significant morbidity and mortality, but the epidemiology in children is not well characterized. OBJECTIVE To describe the epidemiology of SAB in children and adolescents younger than 18 years from Australia and New Zealand. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study, using data from the Australian New Zealand Cooperative on Outcomes in Staphylococcal Sepsis cohort for 1153 children with SAB from birth to less than 18 years in pediatric and general hospitals across Australia and New Zealand, collected between January 1, 2007, and December 31, 2012. Multivariate analysis was performed to identify risk factors for mortality. Incidence calculations were calculated separately for Australasian children younger than 15 years using postcode population denominator data from Australian and New Zealand census data. MAIN OUTCOMES AND MEASURES Demographic data, hospital length of stay, principal diagnosis, place of SAB onset (community or hospital), antibiotic susceptibility and principal antibiotic treatment, and 7- and 30-day mortality. RESULTS Of the 1153 children with SAB, complete outcome data were available for 1073 children (93.1%); of these, males accounted for 684 episodes (63.7%) of SAB. The median age was 57 months (interquartile range, 2 months to 12 years). The annual incidence of SAB for Australian children was 8.3 per 100 000 population and was higher in indigenous children (incident rate ratio, 3.0 [95%CI, 2.4-3.7]), and the incidence for New Zealand children was 14.4 per 100 000 population and was higher in Maori children (incident rate ratio, 5.4 [95% CI, 4.1-7.0]). Community-onset SAB occurred in 761 cases (70.9%), and 142 cases (13.2%) of the infections were methicillin-resistant S aureus (MRSA). Bone or joint infection was most common with 348 cases (32.4%), and endocarditis was uncommon with 30 cases (2.8%). Seven- and 30-day mortality rates were 2.6%(n = 28) and 4.7%(n = 50), respectively. Risk factors for mortality were age younger than 1 year; Maori or Pacific ethnicity; endocarditis, pneumonia, or sepsis; and receiving no treatment or treatment with vancomycin. Mortality was 14.0% (6 of 43) in children with methicillin-susceptible S aureus (MSSA) treated with vancomycin compared with 2.6%(22 of 851) in children treated with alternative agents (OR, 6.1 [95%CI, 1.9-16.7]). MRSA infection was associated with increased length of stay but not mortality. CONCLUSIONS AND RELEVANCE In this large cohort study of the epidemiology of SAB in children, death was uncommon, but the incidence was higher for infants and varied by treatment, ethnicity, and clinical presentation. This study provides important information on the epidemiology of SAB in children and risk factors for mortality.