OBJECTIVES:  The economic burden for individuals with hepatitis C virus (HCV) includes a range of services including high costs for new pharmaceuticals that have demonstrated clinical efficacy. Our primary aim was to evaluate the cost-effectiveness of grazoprevir/elbasvir (GZR/EBR) compared with current therapies for genotypes 1 and 4 chronic HCV. METHODS:  A Markov cohort model was used to calculate cost-effectiveness of GZR/EBR compared to other recommended treatment strategies for chronic HCV over a lifetime horizon from the payer perspective. GZR/EBR was compared against 4 recommended regimens for genotype 1 and against 2 regimens for genotype 4 as well as no treatment. Wholesale acquisition costs were used for drug costs. Annual maintenance costs were used for each one-year cycle specific to the estimated costs of living with the disease at that state and it was assumed that patients treated successfully would maintain the same costs associated with F0-F3 fibrosis. A probabilistic sensitivity analysis (PSA) of 10,000 repetitions was performed with a cost-effectiveness acceptability curve extending willingness-to-pay to $200,000. RESULTS: For Genotype 1 patients, GZR/EBR and LED/SOF were the undominated strategies. The mean costs of 10,000 PSA simulations for GZR/EBR was $90,635 (SD $3,258) and mean effect of 22.99 (SD 0.09) quality-adjusted life years (QALYs) compared to LED/SOF’s mean cost of $127,854 (SD $3,215) and mean effect of 23.24 (SD 0.05) QALYs. For genotype 4 disease, GZR/EBR and PrO/DAS were undominated. GZR/EBR’s mean cost was $89,097 (SD $3,368) compared to PrO/DAS costs of $116,843 ($3,189). GZR/EBR’s mean effect was 23.15 (0.13) QALYs compared to PrO/DAS’s 23.23 (0.07) QALYs. CONCLUSIONS:  Compared to approved and recommended treatment regimens for genotype 1 and 4 HCV disease, GZR/EBR was dominant over no treatment and cost effective compared to other recommended treatments up to a threshold of $151,000 and $322,000 for genotype 1 and 4 disease, respectively.