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Background We performed the first epidemiologic investigation to examine association of demographics and clinical characteristics at diagnosis, as well as health care expense coverage, with survival of US children with aplastic anemia (AA). Methods We obtained electronic medical record data of 1140 children aged 0–19 years diagnosed with AA followed at a pediatric health system between 2004 and 2014. Kaplan–Meier curve and Cox proportional hazards regressions were used. Results Self-pay patients had a mortality risk five times higher than that of those insured by publicly funded insurance (hazards ratio, 95% CI: 6.0, 3.7–9.8). Other features associated with higher mortality risk include pancytopenia (hazards ratio, referent: 4.2, constitutional AA); underweight (2.0, normal-weight); platelet count <50 × 109/l (1.3, ≥50 × 109/l); male sex (1.3, female); and ages at diagnosis 6–11, 11–16 and 16–19 years (1.6, 1.9, 2.3, 1–3 years), respectively. Conclusions Self-pay was the strongest prognostic factor for pediatric AA mortality. Older age, pancytopenia, underweight, male sex and lower platelet count were also associated with increased risk of mortality. These findings may be useful for providers, researchers and policymakers to ensure effective health care delivery to this population and to motivate future etiologic research and establishment of a surveillance registry. [ABSTRACT FROM AUTHOR]