OBJECTIVES: To evaluate the methods and results of published indirect comparison meta-analyses of boceprevir and telaprevir for genotype 1 hepatitis C infection, and to identify methodological issues that can explain the discrepancies in the results of these meta-analyses. METHODS: We searched MEDLINE and EMBASE for indirect comparisons of boceprevir and telaprevier for genotype 1 hepatitis C infection. Following the PRISMA guidelines, we extracted a large set of methodological items. These comprised of inclusion/exclusion criteria, information sources, classification of treatments, and analytic approaches. RESULTS: We identified 4 indirect comparisons. Despite similarly stated eligibility criteria and objectives across these indirect comparisons, we identified discrepancies in the selection of pooled arms and the analytic approaches used, which are most likely to have influenced the differences in the estimated treatment effects. While three of the four studies stratified their analyses by standard-duration therapy (SDT) arms and response-guided therapy (RGT) arms of comparable dose and length of treatment, one study pooled both SDT and RCT therapy together. Three of the four studies used a Bayseian approach, and one used an adjusted Bucher approach. The use of random and fixed effects models also differed between the studies. Furthermore, the type of peg-interferon used (alpha-2a versus alpha-2b) was only given full consideration in 2 of the included studies. Finally, although no study observed statistical differences between boceprevir and telaprevir, the estimated treatment effects differed. CONCLUSIONS: The identified methodological shortcomings and inconsistencies most likely explain the observed discrepancies in findings between the indirect comparisons. Consideration of the methodological differences is necessary when interpreting the results of these studies.