Background: Relapse is a major cause of treatment failure in children with acute myeloid leukemia (AML). The prognosis of children with relapsed AML is poor. Population-based data for this patient group are scarce. The aim of this study was to gain insight into the outcome of Dutch pediatric patients with relapsed AML by describing trends in survival against the background of first-line treatment protocols: ANLL-97 and AML 15 (1998–2009) versus DB AML-01 and NOPHO-DBH-AML-2012 (2010–2018). Material and methods: We retrospectively analyzed outcome and clinical data of all pediatric patients (<18 years) with AML relapse in the Netherlands who were initially diagnosed between 1998 and 2018. Overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan–Meier method. Kaplan-Meier curves and log-rank tests were used to compare survival probabilities of various subgroups. Results: Cumulative incidence of relapse was 38%. Overall, 5-year OS after first relapse was 32% and increased from 23% in 1998‐2009 to 51% in 2010–2018 (P = 0.001). The overall 5-year EFS was 26% and increased from 21% in 1998‐2009 to 33% in 2010–2018 (P = 0.02). In addition to diagnostic period, late relapse (>1 year) was an independent favorable prognostic factor of (event-free) survival. Conclusion: Survival of Dutch pediatric patients with relapsed AML has improved significantly between 1998 and 2018, but remains dismal. Treatment during the period 2010–2018 and late relapse were favorable prognostic factors for OS and EFS.