Hematopoietic cell transplantation (HCT) is the only potentially curative treatment for sickle cell disease (SCD). The probability of event-free survival is currently between 85 and 90% after matched sibling-donor HCT. This intensive treatment conducts to a major change for patients and families. The purpose of the present study was to determine the psychological impact on individuals and their families of this recovery process after HCT. The hypothesis was that the recovery is a process with different aspects (medical, psychological, individual, familial and cultural) which could be discordant. This study was supported by the Etablissement Français des Greffes (EFG) and conducted by child and adolescent psychiatrists, psychologists and a medical anthropologist. The assessment consisted in two semi-structured interviews adressed to the patients and their families for studying their illness narratives and questionnaires for quality of life, post-traumatic stress disorder (PTSD), depression and anxiety. 28 patients (17 males, 11 females) with SCD treated in France by HCT (22 by bone marrow and 6 by cord blood transplantation) and their families were evaluated at least one year (median 5 years, range, 1–14 years) after HCT at the median age of 14 years (range, 4–24 years). Among these 28 patients, 7 had prior history of severe vasculopathy and 6 of stroke before the HCT. At evaluation, 27 patients were free from SCD symptoms (but 3 had moderate chronic GVHD), 1 had graft rejection. 9 patients (4 males, 5 females) (median age 16 years, range 7–23 years) presented psychiatric symptoms as inhibition, depression, hypomaniac symptoms, anxiety, stutter. A psychiatric care was indicated for these 9 subjects. No diagnosis of current PTSD was found. Psychological distress was reported by parents. 21 patients considered themselves as cured, 4 of them in an incomplete way (none with stroke before the HCT, 3 with moderate chronic GVHD), and 3 not cured at all (none with stroke before the HCT, 1 with graft rejection). The study of the narratives illustrated the major individual, familial and cultural changes after the HCT. The recovery needed complex adjustments. Patients had to cope with new potentialities and requirements: school and relationships with peers, identity issues (disease transmission, infertility) and family changes. This study underlies the importance of psychological interventions for improving the outcome of patients with SCD treated by HCT and their families.