Between 1979 and 2004, 167 patients younger than 20 years were treated surgically for humeral or femoral unicameral bone cysts with either injection of corticosteroids (steroids), curettage plus bone grafting (curettage), or a combination injection of steroids, demineralized bone matrix, and bone marrow aspirate (SDB) at Children's Hospital of Boston and Massachusetts General Hospital (mean followup, 7.3 years; range, 1 month-27 years). Outcomes included treatment failure (defined clinically as subsequent pathologic fracture or need for retreatment to prevent pathologic fracture) and complications. Information was obtained from medical records and by telephone questionnaire. After one treatment, 84% of cysts treated with steroids experienced failed treatment versus 64% with curettage and 50% with SDB. For unicameral bone cysts requiring retreatment (regardless of first treatment), 76% retreated with steroids had failed treatment versus 63% with curettage and 71% with SDB. Curettage was associated with the lowest rate of posttreatment pathologic fractures and highest rate of pain and other complications. Multivariate logistic regression indicated treatment with steroids alone and younger age were independent predictors of failure. We believe SDB is a reasonable first treatment for unicameral bone cysts in the humerus and femur in patients younger than 20 years, being less invasive yet comparable to curettage in preventing recurrence.