The quality of emergency department (ED) care for children in the US is highly variable. The National Pediatric Readiness Project aims to improve survival for children receiving emergency services. We conducted a cost-effectiveness analysis of increasing ED pediatric readiness, using a decision-analytic simulation model. Previously published primary analyses of a nationally representative, population-based cohort of children receiving emergency services at 747 EDs in eleven states provided clinical and cost parameters. From a health care sector perspective, we used a 3 percent annual discount rate and quantified lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). We performed probabilistic, one-way, and subgroup sensitivity analyses. Increasing ED pediatric readiness yields 69,100 QALYs for the eleven-state cohort, costing $9,300 per QALY gained. Achieving high readiness nationally yields 179,000 QALYs at the same ICER (with implementation costs of approximately $260 million). Implementing high ED pediatric readiness for all EDs in the US is highly cost-effective.