The use of new megaprosthesis for massive bone loss is an option for the replacement of skeletal segments. There are several clinical scenarios that can be associated with this situation including severe trauma with multiple failed osteosynthesis with a non union or with a previous prosthetic replacement of a neighbouring joint; multiple revision of arthroplasty with or without infections or large resections of tumours. The aim of this work is to evaluate retrospectively both clinical and radiological outcomes and any complications in patients treated with megaprosthesis in SEPTIC BONE DEFECTS in our Hospital from February 2012 to January 2015. From February 2012 to January 2014 a total of 20 patients were treated with mono-and bi-articular megaprosthesis subdivided as follows: 4 proximal femur, 11 distal femur, 3 total femur, 1 total humerus and 1 proximal humerus. Clinical and serial radiographic evaluations were performed at 6 weeks, 3, 6, 12, 18 and 24 months. Blood parameters with CRP and ESR were monitored for at least 2 months. The mean follow-up of patients was about 24.4 months (range 5 months to 31 months). The mean age of the patients was 53 years (range 37–80years). Of the patients 20, 9 were female and 11 were male. The aetiology was: 11 septic non unions, 3 infected TKA, 4 infected THR and 2 infected tumor prostheses. We have evaluated retrospectively both clinical and radiological outcomes of 20 patients. They had large bone defects that threatened the viability of the limb. They were treated with megaprosthesis. Although the mean length of follow-up was only 24.4 months they showed encouraging clinical results, with good articulation of the segments, no somato-sensory or motor deficit and acceptable functional recovery. There were three cases of dislocation, one case with rifampicin toxicity, one case with acute prosthetic infection (case that needed debridement and one case with chronic oral antimicrobial. Megaprosthesis provides a valuable opportunity to restore functionality to patients with highly disabling diseases. The number of complications is not depreciable.