OBJECTIVE To investigate the clinical implications of cysteine-rich angiogenic inducer 61 (CYR61) in Graves' orbitopathy (GO). METHODS Sera from 52 GO patients, 23 Graves' disease (GD) patients, and 20 healthy controls, and orbital fat tissue samples from 12 of 52 GO patients and 8 control subjects were included for analysis. Concentrations of CYR61 were measured from sera with an enzyme-linked immunosorbent assay, and CYR61 mRNA expression levels were evaluated from orbital fat tissue with polymerase chain reaction. RESULTS Serum CYR61 levels were higher in GO patients than in controls (p = 0.001). Patients with active GO showed higher CYR61 levels than those with inactive GO (p < 0.001) or GD (p = 0.004). Expression of CYR61 mRNA was 7.4-fold higher in patients with GO than in healthy controls (p < 0.001). CONCLUSIONS CYR61 could be an adjuvant biomarker associated with the inflammatory activity of GO.