INTRODUCTION. Recently the evolution of prosthesis technology allows the surgeon to replace entire limbs. These special prostheses or megaprostheses were born for the treatment of severe oncological bone loss. Recently, however, the indications and applications of these devices are expanding to other orthopaedic and trauma situations. Since some years we are implanting megaprostheses in non-oncological conditions such as septic post-traumatic failures represented by complex non-unions and critical size bone defects. The purpose of this study is to retrospectively evaluate the clinical outcome of this treatment and register all the complications and infection recurrence. MATERIAL AND METHOD. Between January 2008 and January 2016 we have treated 55 patients with septic post-traumatic bone defects In 48/55 cases we perform a 2 steps procedure: 1° step: resection, debridment, devices removal and antibiotic spacer implantation; 2° step: spacer removal and megaprosthesis implantation. In 7/55 patients in whom all the femur was infected, we performed a one step procedure by the complete removal of the femur and a megaprosthesis (Total Femur) implantation. RESULTS. We obtained good results from a clinical, laboratory and radiological point of view with restoration of the function of the affected limb. Only in 5/55 cases the infection recurred. All the Total Femur megaprosthesis implanted in a one step procedure healed without recurrence of infection. CONCLUSION. Megaprosthesis in severe septic bone loss can be considered, in extreme cases appropriately selected, as an available solution for the orthopedic surgeon. The two steps procedure gives the best results with safety and lower infection recurrence creating a membrane (Chamber Induction Technique) that can protect the prosthesis in a safe environment. We can perform a one step procedure only when all the infected segment is entirely removed. This type of complex surgery must be performed in specialized centers where knowledge and technologies are present