High emergency department (ED) pediatric readiness is associated with improved survival among children receiving emergency care, but state and national costs to reach high ED readiness and the resulting number of lives that may be saved are unknown. To estimate the state and national annual costs of raising all EDs to high pediatric readiness and the resulting number of pediatric lives that may be saved each year. This cohort study used data from EDs in 50 US states and the District of Columbia from 2012 through 2022. Eligible children were ages 0 to 17 years receiving emergency services in US EDs and requiring admission, transfer to another hospital for admission, or dying in the ED (collectively termed at-risk children). Data were analyzed from October 2023 to May 2024. EDs considered to have high readiness, with a weighted pediatric readiness score of 88 or above (range 0 to 100, with higher numbers representing higher readiness). Annual hospital expenditures to reach high ED readiness from current levels and the resulting number of pediatric lives that may be saved through universal high ED readiness. A total 842 of 4840 EDs (17.4%; range, 2.9% to 100% by state) had high pediatric readiness. The annual US cost for all EDs to reach high pediatric readiness from current levels was $207 335 302 (95% CI, $188 401 692-$226 268 912), ranging from $0 to $11.84 per child by state. Of the 7619 child deaths occurring annually after presentation, 2143 (28.1%; 95% CI, 678-3608) were preventable through universal high ED pediatric readiness, with population-adjusted state estimates ranging from 0 to 69 pediatric lives per year. In this cohort study, raising all EDs to high pediatric readiness was estimated to prevent more than one-quarter of deaths among children receiving emergency services, with modest financial investment. State and national policies that raise ED pediatric readiness may save thousands of children's lives each year.