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Outcomes of patients with acute myeloid leukemia (AML) improve significantly by intensification of induction. To further intensify anthracycline dosage without increasing cardiotoxicity, we compared potentially less cardiotoxic liposomal daunorubicin (L-DNR) to idarubicin at a higher-than-equivalent dose (80 vs 12 mg/m² per day for 3 days) during induction. In the multicenter therapy-optimization trial AML-BFM 2004, 521 of 611 pediatric patients (85%) were randomly assigned to L-DNR or idarubicin induction. Five-year results in both treatment arms were similar (overall survival 76% ± 3% [L-DNR] vs 75% ± 3% [idarubicin], P_logrank = .65; event-free survival [EFS] 59% ± 3% vs 53% ± 3%, P_logrank = .25; cumulative incidence of relapse 29% ± 3% vs 31% ± 3%, P_(Gray) = .75), as were EFS results for standard (72% ± 5% vs 68% ± 5%, P_logrank = .47) and high-risk (51% ± 4% vs 46% ± 4%, P_logrank = .45 …