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Introduction: Varicose Veins (VV) are enlarged, convoluted, and elongated veins that primarily affect the superficial veins in the lower limbs and are one of the most prevalent indications of vascular diseases. The reasons for elevated venous pressure are understood, but the inflammatory cytokines that initiate the ultimate pathways of tissue destruction and are in charge of the clinical characteristics of Chronic Venous Insufficiency (CVI) are yet unknown. Although inflammation plays a crucial role in the process of tissue apoptosis, it also plays a crucial role in tissue repair and regeneration. Aim: To investigate changes in blood markers of varicose vein inflammation and endothelial damage and compare them with systemic markers in VV patients and conclude that they are increased in VV blood. Materials and Methods: The comparative cross-sectional study was conducted in the Department of Biochemistry on 70 patients with primary VV who were scheduled for Outpatient Sclerotherapy at Nootan Medical College and Research Centre, Sankalcahnd Patel Vidyadham in Visnagar, Gujarat, India from April 2021 to June 2023. Chronic lower extremity Venous Disease (CVD) was categorised using the Clinical Aetiology Anatomy Pathophysiology (CEAP) classification method. Blood samples were obtained above the knee from the tortuous and dilated varicose tributaries of the great saphenous vein (local) and from the antecubital (systemic) vein by standard venipuncture. Erythrocytes, leukocytes, platelets, haemoglobin, and haematocrit were determined using an automatic haematology analyser. D-dimer and High sensitivity C-reactive Protein (hsCRP) were determined by an immune turbidimetric assay. IL-6 and von Willebrand factor (vWF) were measured by Enzyme Linked Immunosorbent Assay (ELISA) using commercially available kits according to the manufacturers’ instructions. An Independent samples t-test was used to compare group difference, and p-value ≤0.05 were considered significant in all two-sided statistical tests. Results: Basic haematologic test results {systemic versus (vs) varicose blood samples} were comparable. In VV, the following parameters were significantly increased compared to systemic blood: Haemoglobin (12.85±1.81 g/dL vs. 15.82±1.57 g/dL, p