OBJECTIVES This study assesses the PAN-genotypic costs-effectiveness of sofosbuvir compared with standard of care in the Netherlands. METHODS Untreated hepatitis C virus (HCV) infection results in chronic liver disease. The prevalence in The Netherlands is estimated at 0.1-0.4% with 50% of patients having HCV genotype 1 (GT1), 10% GT2, 30% GT3 and 10% GT4-5-6. Current standard of care (SoC), regardless of genotype consists of weekly subcutaneous pegylated interferon-alpha (PegIFN-α) plus daily oral ribavirin. In GT1, the protease inhibitors telaprevir or boceprevir are added. Sofosbuvir (SOF), a novel Direct Antiviral Agent (DAA), has consistently demonstrated high rates of sustained virological response (SVR) when given with ribavirin±PegIFN-α. This cost-effectiveness evaluation is based on a Markov transition model, that combines efficacy and safety data from published RCTs with SOF and SoC in all genotypes with specific attention for subgroups for whom no alternatives are available (no PegIFN-α eligibility). Medical resource use is based on clinical guidelines and expert opinion. Costs include treatment costs, monitoring costs, costs for treatment of complications and adverse events as well as productivity loss. The model has a lifetime horizon and costs are discounted with 4% and outcomes with 1.5%. Results are presented for an HCV mono-infected population with 20% cirrhotic patients.  RESULTS The incremental QALY gain for SOF was 1.23 in PegIFN-α eligible patients and 2.68 in those not eligible for PegIFN-α. The incremental costs were €25,291 for PegIFN-α eligible patients and €89,707 for those not eligible for PegIFN-α. The resulting PAN-genotypic ICERs were €20,487 for PegIFN-α eligible patients and €33,516 for those not eligible for PegIFN-α. CONCLUSIONS PAN-genotypic cost-effectiveness is demonstrated for sofosbuvir in the treatment of HCV in the Netherlands.