Background: The assessment of acute coronary syndrome (ACS) provides useful data not only for identification but also for therapeutic decisions. Objective: To develop a score based on cardiac biomarker for the early diagnosis of ACS patients. Methods: Serum concentrations of myeloperoxidase (MPO) and monocyte chemoattractant protein-1 (MCP-1) beside cardiac troponin I (cTnI) and creatine kinase MB (CK-MB) were measured in a total 200 chest pain patients represented in two groups (estimation and validation). The diagnostics value of biomarkers for discriminating ACS patients was evaluated by area under the receiver-operating characteristic curve (AUC). Multivariate discriminant analysis (MDA) was used to create a predictive score. Results: A novel score depends on a combination of cTnI, CK-MB, MPO, and MCP-1 produces AUCs of 0.93 for discriminating ACS patients and 0.90 for acute myocardial infarction (AMI). This score correctly classified 95% of ACS patients and 93% of AMI patients with good efficiencies were 88.3% and 81%; respectively. This score had similar results in the validation study. Conclusion: Four biomarkers in combination yield a novel score to help in the early and safe prediction of ACS and AMI.