We developed a risk score to predict event-free survival (EFS; the probability of being alive with donor engraftment) after allogeneic hematopoietic cell transplantation for sickle cell disease. The study population (n=1425) was randomly split into training (n=1070) and validation (n=355) cohorts. Cox regression models were built to identify and validate risk factors. Of 9 risk factors evaluated, 2 biologic risk factors were predictive for EFS: age at transplantation and donor type. Based on the training cohort, patients aged ≤12 years with an HLA-matched sibling donor were at lowest risk with 3-year EFS of 92% (95% CI 89-94), score=0. Patients aged ≥13 years with an HLA-matched sibling donor or ≤12 years with an HLA-matched unrelated donor were at intermediate risk (score=1; 3-year EFS 87%, 95% CI 82-91). All other groups, including patients of any age with a haploidentical relative or HLA-mismatched unrelated donor and patients aged ≥13 years with an HLA-matched unrelated donor were high risk (score=2 or 3; 3-year EFS 57%, 95% CI 50-64). These findings were confirmed in the validation cohort. This simple risk score may guide hematologists and patients with sickle cell disease who are considering allogeneic transplantation as a curative treatment relative to other available contemporary treatments.