The cumulative incidence of anthracycline-induced clinical heart failure (A-CHF) in a large cohort of 830 children treated with a mean cumulative anthracycline dose of 288 mg/m2 (median 280 mg/m2; range 15-900 mg/m2) with a very long and complete follow-up after the start of anthracycline therapy (mean 8.5 years; median 7.1 years; range 0.01-28.4 years) was 2.5%. A cumulative anthracycline dose of 300 mg/m2 or more was the only independent risk factor (relative risk (RR)=8). The estimated risk of A-CHF increased with time to 5.5% at 20 years after the start of anthracycline therapy; 9.8% if treated with 300 mg/m2 or more. In conclusion, 1 in every 10 children treated with a cumulative anthracycline dose of 300 mg/m2 or more will eventually develop A-CHF. This is an extremely high risk and it reinforces the need of re-evaluating the cumulative anthracycline dose used in different treatment protocols and to define strategies to prevent A-CHF which could be implemented in treatment protocols.