Background: High quality systematic reviews are the best source of evidence to support healthcare decisions. When the relative effectiveness of two interventions is of interest but no, or very few, trials compare the treatments directly, increasingly, evidence from indirect comparisons may be sought within a review. Indirect comparisons are based on trials that compare one of the two treatments of interest with a third common treatment. To date, several methods exist to undertake indirect comparisons that make various assumptions. A particularly important assumption is that the relative treatment effects of interest are exchangeable across trials. There is debate over whether this assumption, termed exchangeability, can be satisfied and whether results from indirect comparisons are consequently considered to be less reliable than those from direct comparisons. If exchangeability is not satisfied, reviews’ results could be misleading, therefore, it is necessary to assess the quality of the application of published indirect comparisons. Objectives: To systematically review the quality of published indirect comparisons. Methods: Publications that report an indirect comparison of two interventions based on randomised controlled trials were eligible. We searched: The Database of Abstracts and Reviews of Effects [1994 to March 2008]; The Cochrane Database of Systematic Reviews [Issue 1, 2008]; and MEDLINE [1966 to March 2008]. Two independent reviewers will assess eligibility using a form. General information and information concerning quality will be extracted independently by two reviewers for the primary outcome of the review. Assessment criteria have been developed to specifically assess the quality of the published indirect comparisons. The main components of this assessment include: whether the review was systematic in approach; the choice of statistical methodology; how heterogeneity across trials and exchangeability were considered; how direct evidence was sought, included and combined with indirect evidence. We also aim to assess the quality of reporting of the above methods. Results: A description of the identified indirect comparisons and summary of the quality assessment will be presented. Conclusions: Recommendations will be proposed to improve the quality of future applications of indirect comparison methods.