Beta-Thalassemia Major (TM), firstly described by Cooley, is and inherited blood disorder that leads to anaemia due to an imbalanced globin chain synthesis effecting erythroid maturation and red cells survival and requests regular life-long blood transfusions and iron-chelating therapy. Among all the complications and organ diseases, osteopenia and osteoporosis, as progressive diseases are getting important cause of morbidity in a population whose longevity is increasing. The authors describe a case of a 26-year-old female with Beta-Thalassemia Major affected by a subtrochanteric fracture of the right femur on minor trauma. Cardiovascular, endocrinologic and thrombotic pattern leading to bone modifications are reported and Literature reviewed. Fracture was surgically treated with anterograde reconstructive intramedullary locked nail (AFN, Synthes) with 2 distal screws inserted in a static mode.