© 2016 Royal Australasian College of Physicians.Background: Vascular disease is a common cause of death in patients with chronic hepatitis C (CHC) infection; however, the association between CHC and atherosclerosis is unclear. Aims: To determine whether patients with CHC have increased subclinical vascular disease and whether genotype or antiviral treatment modifies this risk. Methods: Fifty CHC patients and 22 age-matched and sex-matched healthy controls underwent clinical and biochemical assessment for vascular risk factors. In addition, vascular risk was assessed by measuring arterial stiffness (aortic augmentation index and carotid-femoral pulse wave velocity (PWV)), endothelial dysfunction (brachial artery flow-mediated dilatation (FMD) and dilatation post-glycerol trinitrate administration) and carotid intima-media thickness (CIMT). Assessment was repeated in subset of CHC patients (n=12) undergoing antiviral treatment 18months after initiation of treatment. Results: Baseline vascular risk factors and measures of arterial stiffness, endothelial dysfunction and CIMT were not different between cases and controls (P > 0.2 for all). Genotype 1 CHC patients had greater endothelial dysfunction with lower FMD (8.2 ± 3.5% vs 10.9 ± 5.2%, P = 0.03) and higher right CIMT (0.6 ± 0.1mm vs 0.5 ± 0.07mm, P = 0.04) compared with non-genotype 1. Patients who achieved sustained virological response (7/12) showed significant improvement in insulin resistance (homeostasis model of assessment of insulin resistance 2.3 ± 1.2 vs 1.8 ± 0.8, P = 0.02) and arterial stiffness (PWV 7.4 ± 1.1m/s vs 6.5 ± 0.6m/s, P = 0.04). Conclusions: Subclinical vascular disease is not greater in CHC subjects compared with controls. However, among CHC subjects, genotype 1 infection is associated with greater endothelial dysfunction and increased carotid-intima medial thickness compared with non-genotype 1 infection. Successful viral eradication may improve insulin resistance and arterial stiffness.