BACKGROUND: Participation in clinical trials is critical for the success of evidence-based healthcare. Much previous research suggests that people take part in clinical trials mostly for altruistic reasons, and that deriving personal benefit is a secondary consideration. PURPOSE: To investigate patients' reasons for deciding whether to take part in clinical trials and the extent to which personal benefit may be a motivating factor. METHODS: A qualitative study utilizing in-depth semi-structured interviews. Participants were 42 men and women who had been asked to participate in clinical trials testing a range of interventions in different conditions, including some who did not participate or withdrew. Trials were based in either primary or secondary care. Interviews were conducted at home. RESULTS: Reasons for taking part were complex and a wide variety of personal considerations were evident. Gaining some personal benefit emerged as an important primary motivation in this group of respondents, whereas altruistic considerations appeared to be largely subsidiary. People who decided not to take part were also mainly concerned about the balance of personal risk and benefit. LIMITATIONS: Public dissemination of the results may have influenced participants' responses. CONCLUSIONS: Achieving target sample sizes for clinical trials may be enhanced by an understanding of what is likely to motivate patients to take part. In this study, respondents identified a range of attractive benefits, such as care in a specialist team with expert staff, active engagement in their health monitoring or care, more frequent or intensive monitoring, and information about the latest research into their condition.