PurposeTo explore the outcome and prognostic factors between inv(16) and t(8;21) disrupt core binding factor (CBF) in acute myeloid leukemia (AML).MethodsThe clinical characteristic, probability of achieving complete remission (CR), overall survival (OS) and cumulative incidence of relapse (CIR) were compared between inv(16) and (8;21).ResultsThe CR rate was 95.2%, 10-year OS was 84.4% and CIR was 29.4%. Subgroup analysis showed that patients with t(8;21) had significant lower 10-year OS and CIR than patients with inv(16). Unexpectedly, there was a trend for pediatric AML receiving five courses cytarabine to have a lower CIR than four courses cytarabine (19.8% vs 29.3%,P= 0.06). Among the cohort of no-gemtuzumab ozogamicin(GO) treatment, inv (16) patients showed a similar 10-year OS (78.9% vs 83.5%;P= 0.69) and an inferior outcome on 10-year CIR (58.6% vs 28.9%,P= 0.01) than those patients with t(8;21). In contrast, inv (16) and t(8;21) patients receiving GO treatment had comparable OS (OS: 90.5% vs. 86.5%,P= 0.66) as well as CIR (40.4% vs. 21.4%,P= 0.13).ConclusionOur data demonstrated that more cumulative cytarabine exposure could improve the outcome of childhood patients with t(8;21), while GO treatment was beneficial to the pediatric patients with inv(16).Supplementary InformationThe online version contains supplementary material available at 10.1186/s12885-023-10965-5.