OBJECTIVES: To evaluate the quality of published cost-effectiveness analyses of biologic disease modifying antirheumatic drugs (bDMARDs) for rheumatoid arthritis (RA), and to identify methodological issues that can explain the discrepancies in the findings of these cost-effectiveness analyses. METHODS: We performed a systematic literature review to identify cost-effectiveness analyses of biologics indicated for RA. We compared the incremental the cost-effectiveness ratios (ICERs), the net health benefits (NHB), the net monitory benefits (NMB), cost-effectiveness acceptability curves (CEACs), and cost-effectiveness frontiers. RESULTS: We observed large discrepancies, which were predominantly due to the use of different information sources on the effectiveness of the considered biologics. First, substantial differences were observed in the ICER, NHB, NMB estimates. When considering the uncertainty associated with the NHB and NMB estimates, i.e. their 95% confidence intervals, differences were still apparent. CEACs and cost-effectiveness frontiers were only reported in a sub-set of the identified publications. Reading from the CEACs and cost-effective frontier graphs, fixed willingness to pay thresholds yielded different probabilities of the considered biologics being cost-effective. CONCLUSIONS: Cost-effectiveness analyses of biologics indicated for RA need to carefully consider the source of information used as model inputs. Future cost-effectiveness analyses need to assess the large number of evidence synthesis studies conducted on the relative effectiveness of biologics when determining the appropriate model inputs.