Background: YKL-40, a glycoprotein, is associated with inflammatory conditions, including endothelial dysfunction and atherosclerosis. This study aimed to assess the significance of YKL-40 levels in the serum in a hemodialysis (HD) population and investigate their connection to cardiovascular disease (CVD) development. Methods: A case-control study was conducted from August 2022 to January 2023, involving 80 participants (30 patients with CVD and chronic HD, 30 patients with chronic HD without CVD, and 20 apparently healthy individuals). Laboratory assessments encompassed kidney function tests (creatinine and urea), serum sodium and potassium levels, Troponin I, highly sensitive C-reactive protein (Hs-CRP), and serum YKL-40 concentrations measured using ELISA. Incidences of CVD events among the patients were documented. Results: Significantly elevated YKL-40 levels were observed in HD patients with CVD compared to HD patients without CVD and the control group (p