Background: Several sickle cell clinical trials have closed due to inability to enroll patients. To limit the early cessation of a proposed clinical trial due to low accrual rates, we sought to better understand barriers and facilitators to enrolling parents of children with sickle cell anemia (SCD) into clinical trials. Procedure: Focus groups (n=3) were conducted with parents/guardians (n=14) who had not previously been recruited for a clinical trial and were not administering hydroxyurea to their children. Results: Three main themes related to barriers to clinical trial enrollment were identified during analysis of focus groups: general barriers to health related research (general mistrust of research studies, emotional and practical concerns), barriers to trial design (randomization), and barriers to hydroxyurea (long term unknown risks, cancer, myelosuppressive effects). Facilitators identified were need for more education, including request for peer education, and improved explanation of clinical trials or study rationale. Conclusion: Engagement of parents/guardians of children with SCD in identifying barriers and facilitators to clinical trial enrollment may be critical to the development of strategies to enhance SCD trial completion. © 2013 Wiley Periodicals, Inc.