The CD40L on activated T cells and platelets may be activating matrix metalloproteinases, inducing procoagulant activity, and be involved in the pathogenesis of acute coronary syndrome (ACS) by promoting plaque rupture in atheroma [ . 1 ] The aim of this work is to assess soluble serum level CD40L to clarify its role in unstable angina (UA). This work included 70 patients suffered from UA who were admitted to coronary care unit (CCU) in National Heart Institute (NHI). All subjects included in the study were evaluated by history, clinical examination, ECG, Routine biochemical investigations, CK total, CK-MB, and Quantitative ELISA for sCD40L. The sCD40L levels were significantly elevated in patients with UA when compared to controls (4.05 ± 1.61 % vs. 1.42 ± 0.63 %, P< 0.001). In multivariate logistic regression analysis, only sCD40L & FBS were efficient as predictors of UA with optimum cutoff value for diagnosis of UA was 2.15 .% Enhanced levels of sCD40L in angina patients, particularly in patients with UA, suggests that CD40L-CD40 interaction may play a role in both the long-term atherosclerotic process and in the triggering of ACS.