Background: Antiplatelet therapy with clopidogrel decreases ischemic complication especially in patients with acute coronary syndromes or after percutaneous coronary interventions. Our study was designed to test the effects of clopidogrel on soluble CD40 ligand(sCD40l) and on high- sensitivity C- reactive protein(hs- CRP) in patients with stable coronary artery disease(CAD). Methods: This is a randomized, double- blind, placebo- controlled study. A total of 73 patients with stable CAD for >6 months were randomized to receive either clopidogrel(loading dose 300 mg followed by 75 mg/d) for 8 weeks or placebo. Soluble CD40 ligand and hs- CRP were measured at baseline and at completion of the study. Results: All patients were on aspirin therapy, and 74% were on statins. Median and interquartile ranges(IQR) of sCD40l decreased from 64 pg/mL(43- 99) at baseline to 53 pg/mL(35- 77) at 8 weeks(P=.03) in the clopidogrel group and remained unchanged in the placebo group(59 pg/mL, IQR 35- 77 vs 55 pg/mL, IQR 35- 78)(P=non significant). Levels of hs- CRP were not affected by therapy and remained unchanged in both groups. Conclusions: In patients with stable CAD, clopidogrel inhibits the release of sCD40l by platelets, which may contribute to the clinical benefit provided by this drug. This, however, does not translate in a reduction of subclinical inflammation, as measured by hs- CRP. Background: Antiplatelet therapy with clopidogrel decreases ischemic complication especially in patients with acute coronary syndromes or after percutaneous coronary interventions. Our study was designed to test the effects of clopidogrel on soluble CD40 ligand (sCD401) and on high- sensitivity C-reactive protein (hs - CRP) in patients with stable coronary artery disease (CAD). Methods: This is a randomized, double-blind, placebo-controlled study. A total of 73 patients with stable CAD for> 6 months were randomized to receive either clopidogrel Results: All patients were on aspirin therapy, and 74% were on statins. All patients were on aspirin therapy, and 74% were on statins. Median and interquartile ranges (IQR) of sCD40l decreased from 64 pg / mL (43-99) at baseline to 53 pg / mL (35-77) at 8 weeks (P = .03) in the clopidogrel group and remained unchanged in the placebo group (59 pg / mL, IQR 35- 77 vs 5 5 pg / mL, IQR 35-78) (P = non significant). Levels of hs- CRP were not affected by therapy and remained unchanged in both groups. Conclusions: In patients with stable CAD, clopidogrel inhibits the release of sCD401 by platelets , which may contribute to the clinical benefit provided by this drug. This, however, does not translate in a reduction of subclinical inflammation, as measured by hs- CRP.