Background: With increasing treatment options for hepatitis C, evidence of comparative effectiveness of these treatment options is required to improve treatment outcomes. The purpose of this study was to evaluate the most recent comparative effectiveness research and suggest future directions for hepatitis C research. Methods: We identified and evaluated the literature on comparative effectiveness research and conducted a literature search for additional studies since the most current review. A review of ongoing clinical trials in hepatitis C was performed to assess how forthcoming research is addressing the research gaps and limitations. Results: Since a comprehensive comparative effectiveness research review by Chou et al new studies have been published, which were mostly consistent with the consensus in the literature. A few of them added to comparative effectiveness research knowledge by addressing issues of the likelihood of sustained virologic response in an older cohort, the effect of genomics and individualizing treatment duration, or the effect of delayed treatment. Research gaps and limitations of the existing comparative effectiveness research and future study needs were well identified in the second study from Chou et al. Some of the gaps and limitations were filled by additional research over the past year, though many of them still remained unanswered. Conclusion: To have complete information on the effectiveness of alternative treatments for hepatitis C virus, further research is needed on results in the general population, the effectiveness of treatment methods such as noninvasive treatment and individualized treatment, and the long-term effects of triple therapies. Additionally, evidence from a real-world setting is lacking. Methodologically thorough and independently funded retrospective research will help to generalize the effectiveness of current therapies for hepatitis C virus.