Objective To investigate the predictive value of serum N-terminal brain natriuretic peptide (NT-proBNP), soluble lectin like oxidized low density lipoprotein receptor-1 (sLOX-1) and histone deacetylase 3 (HDAC3) levels combined in patients with acute myocardial infarction (AMI). Methods AMI patients admitted to the Third People's Hospital of Kaifeng City from November 2021 to February 2024 were retrospective selected as the research subjects (n=155), and divided into improvement group (n=118) and deterioration group (n=37) according to their disease outcomes. Serum levels of NT-proBNP, sLOX-1 and HDAC3 were compared between the two groups at admission and 6h after operation, and their correlation and predictive value were analyzed, and the risk of disease deterioration was analyzed in patients with different levels. Results Serum NT-proBNP, sLOX-1 and HDAC3 in the worsening group were significantly higher than those in the improving group at admission and 6h after operation (P<0.05). Serum NT-proBNP, sLOX-1 and HDAC3 levels at admission and 6h after surgery were positively correlated with the disease outcome of patients (P<0.05). The AUC of the combined prediction of serum NT-proBNP, sLOX-1 and HDAC3 levels at admission and 6h after surgery was 0.895 and 0.928, respectively, which were higher than those predicted by each index alone (P<0.05). The risk of poor prognosis in patients with high levels of serum NT-proBNP, sLOX-1 and HDAC3 at admission and 6h after surgery was 4 to 10 times that of patients with low levels (P<0.05). Conclusion The changes in serum levels of NT-proBNP, sLOX-1, and HDAC3 in AMI patients can serve as effective predictors for evaluating disease outcomes after clinical intervention, and can assist in the clinical assessment of disease outcome.