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We conducted a retrospective, observational, population-based study to investigate the effect of staphylococcal infections on the hospitalization of children in California during 1985–2009. Hospitalized children with staphylococcal infections were identified through the California Office of Statewide Health Planning and Development discharge database. Infections were categorized as community onset, community onset health care–associated, or hospital onset. Infection incidence was calculated relative to all children and to those hospitalized in acute-care facilities. A total of 140,265 records were analyzed. Overall incidence increased from 49/100,000 population in 1985 to a peak of 83/100,000 in 2006 and dropped to 73/100,000 in 2009. Staphylococcal infections were associated with longer hospital stays and higher risk for death relative to all-cause hospitalizations of children. The number of methicillin-resistant Staphylococcus aureus infections increased, and the number of methicillin-susceptible S. aureus infections remained unchanged. Children