Behcet's disease (BD) is a vasculitic and inflammatory disease causing endothelial dysfunction. Irisin is a metabolic hormone related to insulin resistance and endothelial functions. In this study, we investigated the relationship between irisin and carotid intima-media thickness (cIMT), which is a marker of atherosclerosis in patients with BD. 48 patients with BD and 50 healthy individuals were enrolled in the study. Disease severity was evaluated by BD current activity form. Irisin, glucose, insulin, C reactive protein, erythrocyte sedimentation rate and lipid panel were examined in all patients. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was used to calculate insulin resistance. A simple and inexpensive cIMT test was used as indicator of atherosclerosis. cIMT was 0.62 (0.45-1.05) mm in the patients, while it was 0.38 (0.25-0.65) mm in the control group (p<0.001). Irisin value was found to be 197.3 (24.8-834.2) ng/mL in the control group, while it was 85.4 (4.7-471.1) ng/mL in the patient group (p=0.007). There was a negative correlation between irisin level and cIMT (r=-0.511, p<0.001) and HOMA-IR (r=-0.371, p=0.009). Decreased irisin levels (OR 0.996, 95% CI 0.992 to 1.000, p=0.041), male gender (OR 7.634, 95% CI 1.415 to 41.191, p=0.018), and HOMA-IR (OR 2.596, 95% CI 1.451 to 4.643, p=0.001) are independent risk factors for cIMT in patients with BD. We detected a very strong relationship between cIMT, which is an indicator of subclinical atherosclerosis, and decreased irisin levels in patients with BD. BD is characterized by chronic inflammation, and low serum irisin levels in BD may be related to atherosclerosis.