This report will review the evidence for the comparative efficacy of the parenteral and oral route of administration of methotrexate in rheumatoid arthritis to inform a coverage decision. [...] The AGREE (Appraisal of Guidelines for Research and Evaluation) instrument was used to evaluate the quality of the guidelines identified in the literature search.10 The AMSTAR (Assessment of Multiple Systematic Reviews) instrument was used to assess the methodological quality of systematic reviews.11 Parenteral versus Oral Methotrexate for the Treatment of Rheumatoid Arthritis. [...] A total of 11 articles were selected for the four methotrexate topics, and five of the articles were considered relevant to the discussion of route of administration of methotrexate. [...] Based on the results of the study by Braun et al., the authors concluded that the subcutaneous route was more effective than the oral route for methotrexate administration and that if standard oral dosages were not effective, switching to parenteral methotrexate improved the therapeutic effect in patients with early RA.13 Parenteral versus Oral Methotrexate for the Treatment of Rheumatoid Arthriti [...] This systematic review was discussed previously.12 For each recommendation the level of evidence and the grade of recommendation were assessed using the Oxford levels of evidence and the level of agreement by experts was determined.