Purpose: The purpose of this paper is to introduce a case of refractory chronic osteomyelitis of the femoral shaft.Case Report: A 51 year old male suffered from chronic osteomyelitis of the femoral shaft for about 40 years. In the first stage, thorough debridement, extensive lesion resection, antibiotic bone cement spacer and external fixator were applied; in the second stage, the external fixator and bone cement column were changed to femoral bone marrow internal nail combined with femoral locking plate and autologous bone implantation at the broken end under the premise of complete control of inflammation and good health. Finally, the patient was cured and very satisfied with the current state. Conclusion:We report a case of refractory chronic osteomyelitis, which is very rare to have a long history of disease, a large number of fractures, and deformity degree of lower limbs.