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Acute myocardial infarction (AMI) is one of the most serious complications of coronary heart disease. Although morbidity and mortality have been decreasing year by year, acute coronary syndrome still has a high mortality rate and disability rate. To search for accurate and effective biomarkers, we explore the diagnostic and prognostic value of microRNAs (miRNAs) and the monocyte to high-density lipoprotein cholesterol ratio (MHR) in patients with AMI. By referring to the relevant literature, miR-486-5p, miR-451a and miR-21-5p were reportedly altered in the blood of patients with ischemic heart disease. These miRNAs were selected and validated in 40 AMI patients, 22 unstable angina pectoris (UAP) and 22 healthy groups (HC) by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). All patients with AMI underwent primary percutaneous coronary intervention (PCI) and were followed up 3 months after the operation. MHR and miR-451a expression were markedly elevated in plasma samples of AMI patients compared with the UAP and HC groups, but the expressions of miR-486-5p and miR-21-5p were significantly decreased. The expression level of miRNA-451a increased gradually among the three groups (p < 0.05). However, the expression of miRNA-21-5p showed a downward trend (p < 0.05). More importantly, MHR was significantly different before and after PCI in AMI patients (p < 0.05). Receiver operating characteristic (ROC) analysis indicated that MHR, miR-486-5p, miR-451a and miR-21-5p could diagnose and predict AMI. MiR-451a was a more reliable biomarker for AMI diagnosis among these miRNAs. Moreover, the combination of MHR and miRNAs had higher diagnostic value for AMI. We further demonstrated that miR-21-5p had a strong predictive ability for the occurrence of major adverse cardiovascular events (MACE) after 3 months. The results showed that circulating miR-486-5p, miR-451a, miR-21-5p and MHR may play critical roles in the early phase of AMI, and may be used as potential predictors for AMI diagnosis. Importantly, miR-451a was a more reliable biomarker in diagnosing AMI patients. Circulating miR-21-5p may be used as a predictor of MACE occurrence. [ABSTRACT FROM AUTHOR]