Allogeneic hematopoietic cell transplantation (HCT) is the only known therapy to cure sickle cell disease though few patients receive this therapy. We report outcomes after HLA-matched sibling HCT in 68 patients with sickle cell disease, transplanted in 1989 to 2002. Of these, 33 (49%) were transplanted between 1999 and 2002. Median age at transplantation was 10 (range 2–30) years. Hemoglobin SS was the predominant genotype. Indications for HCT were predominately stroke (n=24) and recurrent vaso-occlusive crises (n=24); others included acute chest syndrome, increasing transfusion requirement, progressive iron overload and recurrent priapism. Forty-four patients (66%) received ≥ 10 red blood cell transfusions prior to HCT. Twenty patients (26%) had poor performance scores prior to transplantation. Busulfan and cyclophosphamide was the most frequently used conditioning regimen (n=63, 92%). Fifty-five patients (81%) received bone marrow allografts, 9 patients (13%) received mobilized peripheral blood, 3 patients (4%) received umbilical cord blood, and 1 patient received umbilical cord blood and bone marrow from the same donor. All patients achieved neutrophil recovery and the probability of platelet recovery ≥20,000/ul at day 100 was 93% (95% confidence interval [CI], 86–98)%. The probabilities of grades 2–4 acute graft-versus-host disease (GVHD) at day 100 and chronic GVHD at 5 years were 10% (95% CI, 4–19%) and 22% (95% CI, 12–33%), respectively. Sixty-five of 68 patients are alive after HCT with a median follow up of 5 years. The 5-year probabilities of overall and disease-free survival were 97% (95% CI, 88–100%) and 84% (95% CI, 75–95%), respectively. We defined treatment failure (inverse of disease-free survival) as death from any cause or disease recurrence defined as having a hemoglobin S >50%. Recurrent disease was the predominant cause of treatment failure (n=10). Of these 10 patients, 8 had return of clinical symptoms and the remaining 2 were symptom-free. Among patients with recurrent disease, 5 had received >10 red blood cell transfusions pre-transplant and 1 was reported to have red blood cell alloantibodies. Four patients with recurrent disease were transplanted for stroke and 6 for vaso-occlusive crisis. Nine of 10 patients received busulfan and cyclophosphamide for their conditioning and the remaining patient, total body irradiation 200cGy (single fraction), fludarabine and anti-thymocyte globulin. Three patients died; all deaths occurred more than 100 days after HCT. Causes of death were hemorrhage (n=1), multi-organ failure (n=1) and unknown (n=1). Of the 10 patients with stroke that had magnetic resonance imaging (MRI) of the brain pre- and post-transplant, 8 showed stable disease post transplant, one showed improvement and one had a worsening MRI. Overall survival after HCT for sickle cell disease is excellent, however recurrent disease and chronic GVHD remain a concern. Future studies should focus on strategies aimed at reducing disease recurrence.