Background: The economic impact of extrahepatic manifestations of hepatitis C virus (HCV) infection remains unknown for France. Aim: To estimate the prevalence of extrahepatic manifestations of HCV and the direct medical costs associated with them. Methods: Estimates of 13 extrahepatic manifestations prevalence were obtained from (1) a retrospective data analysis of HCV-infected patients in a specialised centre and the baseline prevalence in the general French population and (2) an international systematic review. Per-patient-per-year costs to treat these manifestations were obtained from the literature, national databases or expert opinion. The impact of achieving HCV cure after anti-viral therapy was applied to the French healthcare costs. Results: Using approach (1), increased prevalence rates in HCV patients compared to the general population were observed for most extrahepatic manifestations. The mean per-patient-per-year cost of these manifestations in the tertiary centre was 3296 € [95% CI 1829; 5540]. In France, HCV-extrahepatic manifestations amounted to a total cost of 215 million (M) € per year [144; 299]. Using approach (2), the mean per-patient-per-year cost was estimated to be 1117 €. The estimated total cost reduction in France associated with HCV cure was 13.9 M€ for diabetes, 8.6 M€ for cryoglobulinemia vasculitis, 6.7 M€ for myocardial infarction, 2.4 M€ for end-stage renal disease and 1.4 M€ for stroke. Conclusion: Extrahepatic manifestations of HCV infection substantially add to the overall economic burden of the disease in France. HCV cure after anti-viral therapy is expected to significantly reduce the total costs of managing these manifestations in France.