Purpose: DREPADO is a randomized controlled trial (RCT) assessing the impact of a pediatric-adult transition program, on the health status of adolescents with sickle cell disease. Using a biopsychosocial approach with three main facets (educational, psychological and social interactions), it constitutes a complex transition program, which is quite difficult to implement. To facilitate the implementation of this complex program, the aim of this ancillary study is to explore barriers and facilitators at the early stages of this implementation. Methods: A qualitative study with semi-structured interviews was conducted, according to COREQ quality criteria, in patients with sickle cell disease who had already experienced the transition to adult care before DREPADO, and healthcare professionals working on the DREPADO RCT. Results: Semi-structured interviews were conducted with patients (n = 12) and healthcare professionals (n = 12) from November 2019 to May 2020. The main barriers identified by patients were time and implication required by this transition program. Healthcare professionals involved in the coordinating center mentioned changes in their working habits and also elements about the RCT regulatory procedures. Main facilitators reported by both patients and healthcare professionals were the positive perception of the transition program design, and especially the home setting for therapeutic education sessions. Conclusion: This study led to the identification of main barriers and facilitators to the implementation of both the DREPADO intervention and RCT. These propositions could also be used to promote other complex public health interventions or/and other randomized controlled trials.