As the outcome for pediatric central nervous system (CNS) malignancies improves, data regarding long term effects and risk of early mortality are needed. Using the Surveillance, Epidemiology, and End Results database, we evaluated the causes of mortality in 5-year survivors of a CNS tumor diagnosed prior to the age of 20 years. Using United States population data, standardized mortality ratios (SMRs) were calculated to compare number of deaths observed to the expected number for the cohort. Cumulative incidence of subsequent malignant neoplasms (SMNs) and standardized incidence ratios of observed to expected SMNs were calculated. 3,627 patients were included in the study. 20-year overall survival (OS) was 85.7 % compared to an expected rate of 98.5 % (p < 0.001). Death from the primary brain tumor accounted for 51 % of deaths, while death from a SMN accounted for 10 % of deaths. Patients were at an increased risk of death due to cardiovascular and cerebrovascular disease (SMRs = 2.5, 95 % confidence interval (CI) 1.2–4.8 and 7.9, 2.6–19.0, respectively). Cumulative incidence of SMN at 30 years was 6.4 % (95 % CI 4.8–7.7). Patients treated after 1986 enjoyed a small improvement in mortality (20-year OS 86.5 vs 83.8 %, p = 0.005). Five-year survivors of a childhood CNS tumor experienced a nearly 13-fold increased risk of death compared to their peers. Patients were at an increased risk of death due to recurrent disease, SMNs, cerebrovascular and cardiovascular events.