We determined the serum levels of soluble CD40 ligand (sCD40L) in patients with chronic coronary artery disease (CAD) and acute coronary syndrome (ACS). Patients with unstable angina (UA) and myocardial infarction (MI) showed significantly higher levels (P < .001) of sCD40L compared with patients with stable angina (SA) and controls; particularly, high levels occurred in patients with UA (UA: 9.23 +/- 2.92, MI: 7.38 +/- 1.05, SA: 4.42 +/- 1.08; control: 4.01 +/- 0.87 ng/mL). There was no significant difference in sCD40L levels between patients with UA and MI or between patients with SA and controls. Levels of sCD40L did not show any significant correlation with peak creatine kinase (CK), CK-MB isoenzyme activity in patients with MI, troponin T serum levels in patients with UA or with culprit vessel (CV) complexity score (CVCS), type of CV lesion, or vessel score in patients with UA or MI. These results suggest that CD40L plays a pathogenic role in triggering ACS.