Whether adding anthracycline to intermediate- or high-dose cytarabine as consolidation is beneficial remains unclear in acute myeloid leukemia (AML). Eligible AML patients in first complete remission were randomly assigned (1:1) to receive either high-dose cytarabine with idarubicin (IA3 + 3) (idarubicin 10 mg/m², d1-3 and cytarabine 2 g/m², every 12 h, d1-3) or high-dose cytarabine (HDAC) (cytarabine 3 g/m², every 12 h, d1-3) regimens as first consolidation. The primary endpoint was the rate of negative measurable residual disease (MRD^-) after first consolidation. Between November 2018 and December 2021, 407 patients were assigned to IA3 + 3 (n = 204) or HDAC (n = 203) groups. MRD^- after first consolidation for IA3 + 3 and HDAC groups was 65.2% (95%CI: 58.6-71.8%) and 53.2% (46.3-60.1%) (P = 0.009). The 3-year cumulative incidence of relapse was 22.6% (95%CI :16.8-29.0%) and 34.0% (27.1-41.1%) (P = 0.014), DFS was 68.4% (61.5-75.3%) and 52.9% (45.4-60.5%) (P = 0.003), OS was 75.5% (69.0-82.1%) and 69.6% (62.4-76.7%) (P = 0.18) and treatment-related mortality was 8.8% (5.2-13.6%) and 13.0% (8.5-18.5%) (P = 0.23) in two groups, respectively. Eighty-seven (43%) and 114 (56%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), respectively (P = 0.006). IA3 + 3 regimen results in deeper remissions and reduces relapse compared to HDAC. This deeper remission improves DFS and translates into treatment advantage, with fewer patients undergoing allo-HSCT. (ClinicalTrials.gov, NCT03620955).