BACKGROUND Hepatitis C virus (HCV) infection may affect lipid metabolism by enhancing the circulating levels of inflammatory cytokines, together with its impact on endothelial function. AIM To evaluate the potential correlation of changes in lipid profile, carotid intima-media thickness (CIMT), and ankle-brachial index with the severity of fibrosis, grades of esophageal varices (EVs), and fibrosis indices. METHODS The study included 240 subjects who were divided into 3 groups; group 1 (n = 90, HCV-related cirrhotic patients with EVs), group 2 (n = 90, HCV-related cirrhotic patients without EVs), and group 3 (n = 60, served as the healthy control group). All patients underwent routine laboratory tests, including a lipid profile assay. Low-density lipoproteins (LDL)/platelet count and platelet/splenic diameter ratios were calculated. Abdominal ultrasonography, CIMT by carotid Doppler, bedside ankle-brachial index (ABI), liver stiffness measurement, and upper gastrointestinal endoscopy were performed. RESULTS Multivariate logistic regression revealed that very-low-density lipoprotein (VLDL) (β = 0.988, odds ratio 2.5, P = 0.001), LDL/platelet count ratio (β = 1.178, odds ratio 3.24, P = 0.001), CIMT (β = 1.37, odds ratio 3.9, P = 0.001), and ABI (β = 2.3, odds ratio 5.9, P = 0.001) were the key variables associated with significant fibrosis, EVs and endothelial dysfunction. CIMT and LDL/platelet count ratio were predictive of advanced fibrosis and EVs at cutoff values of 1.1 mm and 1 mm, respectively, with an area under the curve (AUC) of 0.966 and 0.960 (P = 0.001), while VLDL and ABI at a cutoff of 16.5 mg/dL and 0.94 were predictive of advanced fibrosis and EVs with an AUC of 0.891 and 0.823, respectively (P = 0.001). CONCLUSION CIMT, ABI, VLDL, LDL/platelet count ratio are good non-invasive predictors of advanced fibrosis, presence of EVs, and endothelial dysfunction in liver cirrhosis.