We offer recommendations to reviewers who consider using study designs other than RCTs in their reviews (Table). First, reviewers should assess the availability of RCTs addressing their review question before determining final inclusion criteria. They should search the Cochrane Central Register of Controlled Trials and MEDLINE and contact content experts. Second, when evidence from RCTs is limited, consider the arguments for and against including nonrandomized studies. Reviewers should consider the potential sources of bias and whether they can be minimized with well-conducted nonrandomized studies. Although Deeks and colleagues (3) observed that it is not always possible to predict when observational studies will be biased, certain conditions increase concerns that particular study designs will give misleading results. Are there secular trends in health care delivery that necessitate concurrent comparison groups? Does the disease process fluctuate such that a before–after design might be misleading? Do outcomes involve subjective judgments of patients or clinicians such that blinding of patients or assessors is more important? Similarly, reviewers should consider whether nonrandomized studies are useful to augment information from RCTs (for example, determination of long-term outcomes or testing the generalizability of an intervention to other populations and settings). Third, reviewers must provide an explicit rationale for their decisions to include or exclude various study designs. If nonrandomized study designs are included, how will they inform the review question? Reviewers must consider which specific study designs can provide useful information while adequately protecting against major sources of bias. Any change in inclusion criteria from the original review protocol must be explained and justified. Fourth, the important domains of individual study quality must be considered. Some existing tools address these areas but may need to be modified to facilitate their use and to incorporate topic-specific issues that affect validity. Fifth, reviewers must consider how their inclusion criteria based on study design may affect their conclusions, and the reviewers should discuss the potential impact of possible biases on their conclusions. Sixth, the quality of execution of studies in a body of literature, given specific study designs, should be incorporated into the discussion and conclusions. Are there consistent flaws that might affect the direction or magnitude of benefits or harms?