Objective: To explore the levels of the peripheral blood monocyte-to-high-density lipoprotein cholesterol ratio (MHR), red blood cell distribution width (RDW) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), and analyze their value and clinical significance in the early warning of malignant ventricular arrhythmia (MVA) among patients with acute myocardial infarction (AMI). Methods: A total of 200 patients with AMI were enrolled in this retrospective study. Patients were divided into the MVA group (n=26) and the non-MVA group (n=174) according to the occurrence of malignant ventricular arrhythmia (MVA) within 48 hours after admission. Clinical data were compared between the two groups. Multivariate Logistic regression analysis was used to identify independent risk factors for early MVA in AMI patients. Receiver operating characteristic (ROC) curve analysis was applied to assess the predictive performance of MHR, NT-proBNP and RDW for early MVA. Results: The MVA group presented higher proportions of Killip grade III–IV cases, as well as higher neutrophil count, monocyte count, RDW, NT-proBNP, MHR and D-dimer levels than the non-MVA group (P<0.05), whereas serum potassium levels were lower (P<0.05). Multivariate analysis demonstrated that elevated MHR, NT-proBNP, RDW, D-dimer and Killip grade III–IV were independent risk factors for early MVA (P<0.05). The combination of MHR, NT-proBNP and RDW achieved an AUC of 0.958, a sensitivity of 96.15% and a specificity of 83.91% in predicting early MVA in AMI patients, which was superior to single-index prediction (P<0.05). Conclusion: Elevated MHR, NT-proBNP and RDW can predict the development of early MVA in AMI patients and provide reliable evidence for clinical risk assessment.