Background: The major cause of illness and death is acute myocardial infarction (AMI). Therefore, to reduce death rates, effective and precise diagnostic biomarkers are needed. Objective: The aim of the current study was to evaluate the association between the expression of miRNA-499-5p and the chemokine (C-C motif) ligand 18 (CCL18) in AMI and its related characteristics in Egyptian populations. Patients and methods: A total of 150 participants were separated into 2 groups for a cross-sectional analytical study; AMI group was composed of 75 patients with AMI, whereas the control subjects' group was made up of 75 people who seemed to be healthy. Over a six-month period from March to September 2018, patients were chosen from the Cardiac Care Units at Suez Canal University Hospital and General Hospital. Using 6-Quantitative Real-Time Polymerase Chain Reaction, the expression of miRNA-499-5p in serum was measured. Using an enzyme-linked immunosorbent test, plasma CCL18 is determined. Results: Patients with AMI had considerably higher plasma levels of CCL18 than the control group (236.6 vs. 56.05 ng/mL; P<0.001). Significant P-value indicates a positive correlation between plasma CCL18 and male sex, smoking, heart rate, fasting blood sugar, and cardiac markers. In 89.3% of AMI patients, serum miRNA-499-5p expression was significantly increased by 6.36-fold (P<0.001). Creatine kinase MB and cardiac troponin I both exhibited a positive connection with serum miRNA-499-5p expression (P=0.003 and P=0.002, respectively). Additionally, serum miRNA-499-5p expression and plasma CCL18 showed a positive connection (P=0.004). Conclusion: CCL18 and miRNA 499-5p are potential biomarkers for AMI and possible predictors for the risk of myocardial damage in Egyptians.