Mitoxantrone is believed to maintain anthracycline antitumour activity but be associated with a reduced cardiotoxicity. The aim of this study was to evaluate the evidence for the cumulative incidence of and risk factors for mitoxantrone-induced cardiotoxicity (M-CT) in children treated for childhood cancers. After an extensive literature search, 17 studies were included. The cumulative incidence varied between 0 and 6.7% in the 16 studies evaluating symptomatic M-CT and between 0 and 80% in the 11 studies evaluating asymptomatic M-CT. Risk factors for developing M-CT remain unclear. All studies had serious methodological limitations. In conclusion, children treated with mitoxantrone are at risk of developing M-CT, but due to the low quality of the current evidence, the exact cumulative incidence and risk factors for M-CT remain unclear. It is too early to conclude that in children mitoxantrone is less cardiotoxic than anthracyclines. More well-designed studies are needed to reliably evaluate the incidence of M-CT and its associated risk factors.