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Objectives: To estimate the incidence, clinical characteristics and risk factors for culture-confirmed invasive bacterial infections in England. Design: Prospective, observational, study of all children with positive blood and/or cerebrospinal fluid (CSF) culture over a 3-year period (2009-2011). Setting: All five hospitals within a geographically defined region in southwest London providing care for around 600 000 paediatric residents. Patients: Children aged 1 month to 15 years Main outcome measures: Rates of communityacquired and hospital-acquired invasive bacterial infections in healthy children and those with co-morbidities; pathogens by age group, risk group and clinical presentation. Results: During 2009-2011, 44 118 children had 46 039 admissions, equivalent to 26 admissions per 1000 children. Blood/CSF cultures were obtained during 44.7% of admissions, 7.4% were positive but only 504 were clinically significant, equivalent to 32.9% of positive blood/CSF cultures, 2.4% of all blood/CSF cultures and 1.1% of hospital admissions. The population incidence of culture-confirmed invasive bacterial infection was 28/100 000. One-third of infections were hospital acquired and, of the communityacquired infections, two-thirds occurred in children with pre-existing co-morbidities. In previously healthy children, therefore, the incidence of community-acquired invasive bacterial infection was only 6.4/100 000. Conclusions: Although infection was suspected in almost half the children admitted to hospital, a significant pathogen was cultured from blood or CSF in only 2.4%, mainly among children with pre-existing comorbidities, who may require a more broad-spectrum empiric antibiotic regime compared to previously healthy children. Invasive bacterial infection in previously healthy children is now very rare. Improved strategies to manage low-risk febrile children are required. [ABSTRACT FROM AUTHOR]