The precocious fusion of the proximal humeral epiphysis has been reported in adolescents with thalassemia major. We evaluated the incidence of this skeletal abnormality in two groups of patients characterized by a different timing of the hypertransfusional regimen (i.e., before or after 10 years of age). Precocious epiphyseal fusion was significantly more common among patients who started hypertransfusional regimen after 10 years of age. Starting hypertransfusional regimen since early life may prevent epiphyseal fusion as a result of a permanent block of marrow proliferation.