The objectives of this study were to determine the most advantageous antiviral therapy option for chronic hepatitis C (CHC) (peginterferon alfa + ribavirin (PegIFN + RBV) 48 weeks (F0–F4), peginterferon alfa + simeprevir + ribavirin (PegIFN + SMV + RBV) 24 weeks (F0–F4), peginterferon alfa + sofosbuvir + ribavirin (PegIFN + SOF + RBV) 12 weeks (F0–F4), dasabuvir + ombitasvir/paritaprevir/ritonavir (Dasabuvir + Ombitasvir/ paritaprevir/ritonavir) 12 weeks (F0–F3) and dasabuvir + ombitasvir/ paritaprevir/ritonavir + ribavirin (Dasabuvir + Ombitasvir/paritaprevir/ritonavir + RBV) 12 weeks (F4)) among treatment-naive and treatment-experienced patients (HCV genotype 1) based on the comparison of cost-effectiveness ratios and economic outcomes (“budget impact” analysis) from implementing the treatment strategy PegIFN-α + SOF + RBV instead of PegIFN-α + RBV, PegIFN-α + SIM + RBV and Dasabuvir + Ombitasvir/paritaprevir/ritonavir. Model-based pharmacoeconomic analysis has been conducted. The costeffectiveness analysis showed that independently of the former treatment experience of CHC (genotype 1) patients the combination PegIFN-α + SOF + RBV was a predominant regimen as compared to PegIFN-α + RBV and PegIFN-α + SMV + RBV. In the groups of patients without cirrhosis and with cirrhosis the highest QALY value was noted for Dasabuvir + Ombitasvir/ paritaprevir/ritonavir and Dasabuvir + Ombitasvir/paritaprevir/ritonavir + RBV combinations, respectively. Also a smaller cost-effectiveness ratio (CER) relative to the two above regimens was noted for PegIFN-α + SOF + RBV. In the group of treatment-naive patients without cirrhosis incremental costeffectiveness ratio (ICER) of Dasabuvir + Ombitasvir/paritaprevir/ritonavir vs PegIFN-α + SOF + RBV was higher than willingness-to-pay threshold (WPT), whereas in the group of patients with cirrhosis ICERDasabuvir + Ombitasvir/paritaprevir/ritonavir + RBV vs PegIFN-α + SOF + RBV was lower than WPT. Using “budget impact” analysis it was shown that switching to PegIFN-α + SOF + RBV from PegIFN-α + RBV regimen will involve extra direct costs for antiviral treatment (AVT), but will lead to a reduction in medical aid costs to the patients not reaching SVR, patients with CHC complications and, as a consequence, will lead to a reduction in cumulative medical costs. Moreover, transition from PegIFN-α + SMV + RBV, Dasabuvir + Ombitasvir/paritaprevir/ ritonavir and Dasabuvir + Ombitasvir/paritaprevir/ritonavir + RBV to PegIFN-α + SOF + RBV will lead to a reduction in both AVT costs and cumulative medical costs.