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Appropriate medication prescribing may be influenced by a prescriber's ability to understand and interpret medical research. The objective of this review was to synthesize the research related to prescribers' critical appraisal knowledge and skills—defined as the understanding of statistical methods, biases in studies, and relevance and validity of evidence.We searched PubMed and other databases from January 1990 through September 2015. Two reviewers independently screened and selected studies of any design conducted in the United States, the United Kingdom, or Canada that involved prescribers and that objectively measured critical appraisal knowledge, skills, understanding, attitudes, or prescribing behaviors. Data were narratively synthesized.We screened 1204 abstracts, 72 full-text articles, and included 29 studies. Study populations included physicians. Physicians' extant knowledge and skills were in the low to middle of the possible score ranges and demonstrated modest increases in response to interventions. Physicians with formal education in epidemiology, biostatistics, and research demonstrated higher levels of knowledge and skills. In hypothetical scenarios presenting equivalent effect sizes, the use of relative effect measures was associated with greater perceptions of medication effectiveness and intent to prescribe, compared with the use of absolute effect measures. The evidence was limited by convenience samples and study designs that limit internal validity.Critical appraisal knowledge and skills are limited among physicians. The effect measure used can influence perceptions of treatment effectiveness and intent to prescribe. How critical appraisal knowledge and skills fit among the myriad of influences on prescribing behavior is not known.