AIM Our aim was to undertake a systematic review of the relevant literature relating to the barriers, modifiers and benefits involved in participating in randomised controlled trials of cancer therapies as perceived by health professionals and patients. METHODS A scoping review was conducted to identify existing systematic reviews in the area of patient participation in clinical trials. Potentially relevant reviews were identified, data extracted and quality assessed. On assessment of the methodology of the existing reviews it was felt that Prescott et al1 was sufficiently rigorous to form a basis for the early research literature (searches ended in 1996). Once the full search strategy for primary studies had been agreed a range of databases were searched from 1996. Unpublished research or research published within grey literature was sought, clinical experts were contacted and bibliographies of retrieved articles were examined. There was no restriction of study by country of origin, or language. Studies that aimed to identify barriers to, moderators of and benefits arising from participation in randomised controlled trials in cancer from the physician or patient perspective were included. All study designs were acceptable provided relevant outcomes were reported. Included papers were assessed for methodological quality using instruments appropriate to the study design. Two reviewers were involved in the selection of studies, data extraction and quality assessment processes, with any disagreements resolved by a third reviewer. Findings are reported as a narrative summary and in tabular form with full data extraction tables and quality assessment tables included in appendices. Studies are grouped according to their perspective (healthcare professional or patient) and whether they describe recruitment to real trials or attitudes to recruitment to trials in general. RESULTS A total of 12,816 references were identified from literature searches with 56 studies published in 58 papers finally selected for inclusion in the review. The included studies represented both the patients’ and the health professionals’ perspectives. The health professionals in these studies included doctors, nurses and Clinical Research Associates. Several themes emerged from the research literature. From the patient perspective there were issues of treatment preference and the uncertainty patients feel about participating in trials. The role of knowledge and information was examined as was the need to time the request for trial participation more carefully. A range of sociodemographic and practical barriers to trial participation were identified alongside issues concerning the benefits of participating in trials. From the health professional perspective a range of system-related and organisational barriers were identified, barriers inherent in a trial’s design and barriers connected with the attitudes of individual health professionals. Although a range of barriers to trial participation were identified, a number of threats to the internal and external validity of the included studies limited interpretation of the evidence. In particular it was found that the issues identified in many of the studies could be, at least partially, an artefact of the research design, the methods of data collection or data analysis. CONCLUSIONS The methodological limitations of the primary studies identified by this review do not allow a clear interpretation of the barriers, moderators and benefits involved in trial participation as perceived by patients and health professionals. It is necessary to be cautious in stating what is and is not a barrier to trial participation. Instead it is concluded that the particular interplay of barriers, modifiers and benefits relevant to participation in cancer trials needs to be prospectively identified by trialists in the light of the themes identified in the literature. Checklists to guide this process are included in this report.