Cyclophilin A is a secreted molecule that has a physiological and pathological role in cardiovascular diseases. However, limited information is available on the relationship between cyclophilin A concentration and acute coronary syndromes (ACS). We investigated whether cyclophilin A concentration is related to the stability of coronary atherosclerotic plaque in patients with ACS.This study included normal controls (n=50), patients with stable angina (SA) (n=60) and patients with ACS, including unstable angina (UA) (n=60) and acute myocardial infarction (AMI) (n=90). Serum soluble cyclophilin A, matrix metalloproteinase 9 (MMP-9), MMP-3 and C-reactive protein concentrations (CRP) were measured. All coronary stenosis were assessed by angiographic coronary stenosis morphology.Serum cyclophilin A concentration in ACS (UA and AMI ) subjects were significantly higher than those in patients with SA and controls (p<0.05). Serum cyclophilin A correlated positively with serum MMP-3 and MMP-9 and CRP in ACS patients(r 1 =0.69, r 2 =0.52, r 3 =0.49 p<0.0001), but not in control. Furthermore, the increased cyclophilin A concentrations was associated with the number of complex coronary stenoses (r 1 =0.63, p<0.0001), but not smooth lesions or stenosis severity, in coronary artery disease patients. Logistic regression analysis also demonstrated that serum cyclophilin A concentration was an independent predictor factor for ACS( OR, 2.721, 95% CI 1.563–4.042, p=0.001).Patients with ACS showed that increased concentrations of cyclophilin A may be a valuable marker for predicting the severity of ACS.