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Objective: Serum YKL-40 plays roles in inflammatory and vascular processes. Our aim was to evaluate serum YKL-40 levels in patients with ankylosing spondylitis (AS) and to investigate their potential relationship with arterial stiffness based on carotid-femoral pulse wave velocity (CF-PWV). Methods: Forty-three patients with AS and 41 healthy controls with no history or current signs of cardiovascular disease were included in the study. All patients were administered nonsteroidal anti-inflammatory drugs (NSAIDs), and none were prescribed anti-tumor necrosis factor agents. Serum YKL-40 levels were measured. CF-PWV and intima-media thickness of the common carotid artery (IMT-C) were evaluated. Results: The mean age of AS patients was 34.6 ± 10.2 years and of controls was 36.3 ± 9.0 years. CF-PWV was significantly higher in AS patients than in controls (8.2±2.7 vs.7.0±1.6 m/s, respectively; P=0.015). However, the IMT-C was not significantly different between AS patients and controls (0.6±0.3 vs. 0.5±0.2 mm, P=0.501). YKL-40 levels were significantly higher in AS patients than in controls (78.9±37.9 vs. 58.4±21.2 ng/mL, P=0.003) and were strongly correlated with CF-PWV (r=0.773, P < 0.001) and IMT-C (r=0.548, P < 0.001). A multiple linear regression analysis revealed that CF-PWV could be explained by serum YKL-40 levels and IMT-C (adjusted R²= 0.707, P=0.013 and P=0.001, respectively). AS patients with a higher disease activity score had higher YKL-40 levels, IMT-C, and CF-PWV than did those with a lower disease activity score (P < 0.001, P=0.008, and P < 0.001, respectively) Conclusion: AS patients had higher serum YKL-40 levels, CF-PWV, and IMT-C than did healthy controls. Additionally, there was an association between increased CF-PWV and serum YKL-40 levels. Therefore, we conclude that CF-PWV and YKL-40 levels may be used for early diagnosis of atherosclerosis in AS patients.