Background: Recruitment of participants into research studies, especially individuals from minority groups, is challenging; lack of diversity may lead to biased findings. Aim: To explore beliefs about research participation among individuals who were approached and eligible for the GRADE study. Methods: In-depth qualitative telephone interviews with randomized participants (n = 25) and eligible individuals who declined to enroll (n = 26). Results: Refusers and consenters differed in trust and perceptions of risk, benefits and burden of participation. Few participants understood how comparative effectiveness research differed from other types of trials; however, some features of comparative effectiveness research were perceived as lower risk. Conclusion: We identified facilitators and addressable barriers to participation in research studies.