BACKGROUND: Bacteremia is now an uncommon presentation to the children’s emergency department (ED) but is associated with significant morbidity and mortality. Its evolving etiology may affect the ability of clinicians to initiate timely, appropriate antimicrobial therapy. METHODS: A retrospective time series analysis of bacteremia was conducted in the Alder Hey Children’s Hospital ED between 2001 and 2011. Data on significant comorbidities, time to empirical therapy, and antibiotic susceptibility were recorded. RESULTS: A total of 575 clinical episodes were identified, and Streptococcus pneumoniae (n = 109), Neisseria meningitidis (n = 96), and Staphylococcus aureus (n = 89) were commonly isolated. The rate of bacteremia was 1.42 per 1000 ED attendances (95% confidence interval: 1.31–1.53). There was an annual reduction of 10.6% (6.6%–14.5%) in vaccine-preventable infections, and an annual increase of 6.7% (1.2%–12.5%) in Gram-negative infections. The pneumococcal conjugate vaccine was associated with a 49% (32%–74%) reduction in pneumococcal bacteremia. The rate of health care–associated bacteremia increased from 0.17 to 0.43 per 1000 ED attendances (P = .002). Susceptibility to empirical antibiotics was reduced (96.3%–82.6%; P < .001). Health care–associated bacteremia was associated with an increased length of stay of 3.9 days (95% confidence interval: 2.3–5.8). Median time to antibiotics was 184 minutes (interquartile range: 63–331) and 57 (interquartile range: 27–97) minutes longer in Gram-negative bacteremia than in vaccine-preventable bacteremia. CONCLUSIONS: Changes in the etiology of pediatric bacteremia have implications for prompt, appropriate empirical treatment. Increasingly, pediatric bacteremia in the ED is health care associated, which increases length of inpatient stay. Prompt, effective antimicrobial administration requires new tools to improve recognition, in addition to continued etiological surveillance.