Background: Our objectives were to review the economic modelling methods and cost-effectiveness of secondgeneration direct-acting antiviral agents for the treatment of chronic HCV infection. Methods: A systematic literature search was performed in February 2017 using Scopus and OVID to review relevant publications between 2011 to present. Two independent reviewers screened potential papers. Results: The database search resulted in a total of 1,536 articles; after deduplication, title/abstract and full text screening, 67 studies were included for qualitative analysis. The vast majority of studies were conducted in high-income countries (n=59) and used Markov-based modelling techniques (n=60). Most of the analyses utilized long-term time horizons; 58 studies calculated lifetime costs and outcomes. The examined treatments were heterogenic among the studies; seven analyses did not directly evaluate treatments (just with screening or genotype testing). The examined treatments (n=60) were either dominant (23%), or cost-effective at base case (57%) or in given subgroups (18%). Only one (2%) study reported that the assessed treatment was not cost-effective with the given setting and price. Conclusions: Despite their high initial therapeutic costs, second-generation direct-acting antiviral agents were found to be cost-effective to treat chronic HCV infection. Studies were predominantly conducted in higher income countries, although we have limited information on costeffectiveness in low-and middle-income countries, where assessment of cost-effectiveness is even more essential due to more limited health-care resources and potentially higher public health burden due to unsafe medical interventions.