Cytokines play a key role in the pathogenesis of coronary artery disease (CAD). The aim of current study was to investigate the relationship between the serum concentrations of 12 cytokines with mortality and extent of CAD in individuals undergoing angiography and healthy controls. 342 CAD patients were recruited and divided into 2 groups: those with ≥50% occlusion in at least one coronary artery [Angiography (+)] or <50% obstruction in coronary arteries [Angiography (-)]. Also 120 healthy subjects were enrolled as control group. Lipid profile, fasting blood glucose, body mass index, and blood pressure were evaluated in all the subjects. An Evidence Investigator® was used for measuring 12 cytokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, MCP-1, IFN-γ, EGF, VEGF) using sandwich chemiluminescent assays. Univariate analysis, multivariate regression models, ROC, and Kaplan-Meier survival curves were used for exploring the candidate markers in CAD patients. Serum level of IFN-γ, IL-4, MCP-1, EGF, IL-6, and IL-8 were markedly higher in angiogram-positive patients, while VEGF concentrations were significantly (P 2.16 pg/mL IL-6 had a > 94% sensitivity and 70% specificity in predicting 2 years mortality in the subjects with a serum MCP-1 > 61.95 pg/ mL, and patients having IL-6/MCP-1 combination had a shorter survival.Our findings demonstrate that CAD patients with serum MCP-1 and IL-6 levels of >61.95 and >2.16 pg/mL had a higher mortality with 94.1% sensitivity and 70.5% specificity for predicting mortality in CAD patients.