OBJECTIVES: Hepatitis C is a blood-borne liver infection caused by the hepatitis C virus that can be spread through the sharing of needles, inadequate sterilization of medical equipment, blood transfusions, and sexual transmission. The costs and expenditures related to hepatitis C infection are estimated to be more than $600 million annually. This study is a systematic review that includes all the pharmacoeconomic literature available to-date to assess if ledipasvir/sofosbuvir is more cost-effective than other current medications in the treatment of Hepatitis C. METHODS: A systematic review was conducted by searching PubMed, MEDLINE, and other journals to identify relevant studies. Some inclusion criteria included cost effective analysis studies, if drug costs were considered, and inclusion of quality-adjusted life years gained (QALYs). Some exclusion criteria included studies in languages other than English, if it was published before the year 2014, and if it focused on co-morbidity with HIV. The cost-effectiveness measured involved direct medical costs. Indirect medical costs and costs due to loss of productivity were not included. The costs of drug treatments were determined using wholesale acquisition costs, with daclatasvir costs being estimated, as data was not available. Sensitivity analyses performed include 1-way sensitivity analyses and probabilistic sensitive analysis. RESULTS: CONCLUSIONS: According to the pharmacoeconomic studies reviewed, ledipasvir/sofosbuvir is determined to be the most cost-effective drug for genotypes 1 and 4 with the possibility of being cost-effective for genotype 3.