OBJECTIVES: The aims of our multicenter study were to quantify direct medical costs during interferon (IFN)-based antiviral treatment and per sustained virological response (SVR) among patients with chronic hepatitis C-virus (HCV) infection and advanced hepatic fibrosis in the Netherlands, Germany, Switzerland and Canada.  METHODS: Direct medical costs were quantified during IFN-based treatments received by all consecutive patients (N=455) with chronic HCV infection and biopsy-proven bridging fibrosis or cirrhosis (Ishak scores 4-6). The components of care from initiation of therapy were quantified by three distinct categories: treatment, safety-monitoring and complications. Total medical costs attributable to each cost component were calculated and expressed in 2013 Euros. Sensitivity analyses were performed to explore the influence of components of care and the SVR rate on medical costs. RESULTS: In total, 672 IFN-based treatments, administered to 455 patients, were included in the analysis. At time of inclusion, median age was 48 years (IQR 43–56), 317 (70%) patients were male, and 346 (76%) presented with cirrhosis. Platelet counts were available for 432 (95%) patients, of whom 226 (52%) had thrombocytopenia. Total mean medical costs per treatment were €14,559 (95% CI, €13,323-€15,836). Among patients with a normal platelet count and thrombocytopenia, mean costs were €12,419 (95%CI, €10,974-€13,937) and €14,416 (95%CI, €12,503-€16,598), respectively. The costs per SVR were €26,105 (95%CI, €23,068-€29,296) for patients with normal platelet counts and €50,907 (95%CI, €44,151-€59,612) for patients with thrombocytopenia. In patients with severe thrombocytopenia (platelet count below 100*109/L) the costs per SVR were €74,961 (95%CI, €55,463-€103,541). The corresponding SVR rates were 48%, 28% and 18%, respectively. Sensitivity analyses confirmed the robustness of our results.  CONCLUSIONS: Real-world medical costs did not differ significantly among patients with or without thrombocytopenia. However, the SVR rate was lower among patients with severe thrombocytopenia, in whom the medical costs per SVR with IFN-based therapy were substantial.