Individuals with CF and their parents cite safety concerns as barriers to participating in clinical studies. We assessed whether a brochure/infographic describing patient safety monitoring processes could reduce knowledge and attitude barriers regarding safety monitoring. We also identified factors associated with likely participation in future CF studies. Respondents from three CF centers in the U.S. were randomly assigned to receive the safety monitoring brochure/infographic or an unrelated brochure. Fifty parents of children with CF <16, 50 adolescents with CF 16–21, and 50 adults with CF ≥22 years old were recruited to complete the study survey. Factors associated with survey responses and with reported likelihood of participating in future studies were assessed. Overall the safety monitoring brochure/infographic was associated with increased likelihood of future participation in non-drug studies (aOR 2.30, CI95 1.01–5.28), but not in drug studies. Non-Hispanic respondents reported greater likelihood of participating in a future drug study than Hispanic respondents (aOR 3.18, CI95 1.30–7.74). Adults with CF (aOR 2.62, CI95 1.05–6.51) and parents (aOR 4.49, CI95 1.66–12.15) were more likely than adolescents to report they would ask their care team about clinical trials. Confidence in safety monitoring was associated with reported likelihood of future participation in drug studies. Potential future participation in CF drug and/or non-drug studies was associated with respondent age and ethnicity, receiving the safety monitoring brochure/infographic, and confidence in safety monitoring. Our findings underscore the need for education about safety monitoring, with targeted approaches for the Hispanic CF population and adolescents. •Safety concerns are a barrier to clinical trial participation in the CF community•A safety brochure did not increase reported future participation in clinical trials•Hispanic individuals were less likely to report future drug study participation•Adolescents reported lower likelihood of asking the care team about clinical trials•Confidence in safety monitoring predicts likelihood of drug study participation