Aim: The aim is to evaluate serum cysteine-rich protein 61 (Cyr61) levels in patients with coronary artery disease (CAD). Patients & methods: Serum Cyr61 levels were measured in 180 patients with CAD and 74 participants without CAD. Results: Serum Cyr61 levels were significantly higher in CAD patients. Patients with acute coronary syndrome showed significantly higher Cyr61 than those with stable angina pectoris. Serum Cyr61 levels in complex lesion group were significantly higher. Serum Cyr61 was positively correlated with Gensini score and C-reactive protein. Multivariable logistic regression analyses demonstrated that serum Cyr61 levels were independently correlated with the existence of CAD (p = 0.01). Conclusion: Our study suggested Cyr61 as a potential biomarker in characterizing CAD and therapeutic target for CAD.