Abstract Background 5-Azacytidine (AZA) combined with the BCL2 inhibitor Venetoclax (VEN) is the standard treatment for elderly acute myeloid leukemia (AML) patients or those who are unfit for intensive chemotherapy (elderly or unfit AML). However, an effective and rapid predictive biomarker to predict treatment outcome remains elusive. Methods miR-182 promoter methylation was measured in 94 AZA + VEN-treated elderly or unfit AML patients and 20 normal controls (NCs) samples. To determine whether miR-182 promoter methylation is a predictive marker of clinical outcomes in AZA + VEN-treated AML patients in a real-world setting, we analyzed and compared the complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate, overall survival (OS), and leukemia free-survival (LFS) across different methylation groups: miR-182 promoter hypomethylation (median value 20.21%) in a retrospective study. Results The average methylation frequency was markedly higher in 94 AZA + VEN-treated elderly or unfit AML patients than that in 20 NCs. However, some AML patients (11.7%) still presented low miR-182 promoter methylation (