Objective: This study compared the cost-effectiveness of direct-acting antiviral therapies currently recommended for treating genotypes (GT) 1 and 4 chronic hepatitis C (CHC) patients in the US.Methods: A cost-effectiveness analysis of treatments for CHC from a US payer's perspective over a lifelong time horizon was performed. A Markov model based on the natural history of CHC was used for a population that included treatment-naive and -experienced patients. Treatment alternatives considered for GT1 included ombitasvir/paritaprevir/ritonavir+dasabuvirribavirin (3DR), sofosbuvir+ledipasvir (SOF/LDV), sofosbuvir+simeprevir (SOF+SMV), simeprevir+pegylated interferon/ribavirin (SMV+PR) and no treatment (NT). For GT4 treatments, ombitasvir/paritaprevir/ritonavir+ribavirin (2D+R), SOF/LDV and NT were compared. Transition probabilities, utilities and costs were obtained from published literature. Outcomes included rates of compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC) and liver-related death (LrD), total costs, life-years and quality-adjusted life-years (QALYs). Costs and QALYs were used to calculate incremental cost-effectiveness ratios.Results: In GT1 patients, 3D +/- R and SOF-containing regimens have similar long-term outcomes; 3D +/- R had the lowest lifetime risks of all liver disease outcomes: CC =30.2%, DCC = 5.0%, HCC = 6.8%, LT =1.9% and LrD =9.2%. In GT1 patients, 3D +/- R had the lowest cost and the highest QALYs. As a result, 3D +/- R dominated these treatment options. In GT4 patients, 2D+R had lower rates of liver morbidity and mortality, lower cost and more QALYs than SOF/LDV and NT.Limitations: While the results are based on input values, which were obtained from a variety of heterogeneous sourcesincluding clinical trials, the findings were robust across a plausible range of input values, as demonstrated in probabilistic sensitivity analyses.Conclusions: Among currently recommended treatments for GT1 and GT4 in the US, 3D +/- R (for GT1) and 2D+R (for GT4) have a favorable cost-effectiveness profile.