Background and Aim Behçet disease (BD) is a rare chronic relapsing-remitting inflammatory systemic vasculitis. BD patients were reported to have marked acceleration of subclinical atherosclerosis (SCA). Endocan is a soluble proteoglycan mainly secreted by the activated endothelium. The present study aimed to assess the relation between serum endocan levels and SCA in BD patients. Subjects and Methods The study included 40 adult BD patients in addition to twenty age- and sex-matched healthy controls. BD was diagnosed according to International Study Group criteria. Upon recruitment, all participants were subjected to careful history taking and thorough clinical examination. BD activity was assessed using Behçet Syndrome Activity Score. Measurement of serum endocan was performed using quantitative double-antibody sandwich ELISA kit. CIMT measurement was done using B-mode ultrasound. Results Comparison between patients and controls regarding serum endocan levels revealed significantly higher endocan levels in BD patients [median (IQR): 155.0 (69.3–610.0) versus 73.8 (51.9–94.6)]. Using ultrasound assessment, SCA was found in 14 BD patients (35.0%). Comparison between patients with SCA and patients without regarding the clinical and laboratory data revealed that the former group had significantly higher CRP [median (IQR): 36.5 (26.8–43.5) versus 21.0 (11.8–26.8) mg/dL, p < 0.001] and endocan [median (IQR): 622.0 (107.4–974.8) versus 104.5 (64.0–342.0) mg/dL, p = 0.004] levels. Logistic regression analysis recognized endocan [OR (95% CI): 1.0 (1.0–1.012), p0.035] levels as significant predictor of SCA in multivariate analysis. Conclusion The present study identified the clinical value of serum endocan levels as a possible early marker of vascular involvement in BD patients.