OBJECTIVES: To compare the prevalence, resource utilization, and mortality for pediatric severe sepsis identified using two established identification strategies. DESIGN: Observational cohort study from 2004 to 2012. SETTING: Forty-four pediatric hospitals contributing data to the Pediatric Health Information Systems database. PATIENTS: Children 18 years old or younger. MEASUREMENTS AND MAIN RESULTS: We identified patients with severe sepsis or septic shock by using two International Classification of Diseases, 9th edition, Clinical Modification-based coding strategies: 1) combinations of International Classification of Diseases, 9th edition, Clinical Modification codes for infection plus organ dysfunction (combination code cohort); 2) International Classification of Diseases, 9th edition, Clinical Modification codes for severe sepsis and septic shock (sepsis code cohort). Outcomes included prevalence of severe sepsis, as well as hospital and ICU length of stay, and mortality. Outcomes were compared between the two cohorts examining aggregate differences over the study period and trends over time. The combination code cohort identified 176,124 hospitalizations (3.1% of all hospitalizations), whereas the sepsis code cohort identified 25,236 hospitalizations (0.45%), a seven-fold difference. Between 2004 and 2012, the prevalence of sepsis increased from 3.7% to 4.4% using the combination code cohort and from 0.4% to 0.7% using the sepsis code cohort (p < 0.001 for trend in each cohort). Length of stay (hospital and ICU) and costs decreased in both cohorts over the study period (p < 0.001). Overall, hospital mortality was higher in the sepsis code cohort than the combination code cohort (21.2% [95% CI, 20.7-21.8] vs 8.2% [95% CI, 8.0-8.3]). Over the 9-year study period, there was an absolute reduction in mortality of 10.9% (p < 0.001) in the sepsis code cohort and 3.8% (p < 0.001) in the combination code cohort. CONCLUSIONS: Prevalence of pediatric severe sepsis increased in the studied U.S. children's hospitals over the past 9 years, whereas resource utilization and mortality decreased. Epidemiologic estimates of pediatric severe sepsis varied up to seven-fold depending on the strategy used for case ascertainment.