Background: Acute coronary syndromes (ACS) is the highest risk of fatality worldwide, cardiac troponins and creatine kinase are widely used clinically in diagnosis of ACS, but they have some limitations .Thus, there is a need to find a novel biomarker with higher accuracy. This work aimed to assess the predictive potential of serum miR-183-5p and miR-208b expression in acute coronary syndrome. Method: The expression levels of serum miRNA-183-5p and miRNA-208b were evaluated by quantitative real-time polymerase chain reaction in 52 patients with acute myocardial infarction (AMI), 23 unstable angina (UA) patients, and 25 healthy volunteers. Results: Mir-183-5p and miR -208b expression levels were significantly upregulated in serum of unstable angina and AMI patients compared to normal controls (p<0.001). In addition, only miR-208b expression levels was over-expressed in unstable angina patients compared to the control group (p=0.044). Mir-183-5p had diagnostic value for AMI at cut off point of ≥8.03 with a sensitivity and specificity of 92% and 73%, respectively. While, miR- 208b had sensitivity of 96% and specificity of 60% at a cut-off point of ≥2.09. Conclusion: Mir-183-5p could be used as a non-invasive biomarker to that could detect ACS early and discriminate AMI patients and this could improve health outcome.