The most common reconstruction method for bone defects caused by giant cell tumor of bone (GCTB) is cement packing combined with subchondral bone grafting and extra fixation. However, this method has several limitations involving bone cement and bone graft, which may lead to poor prognosis and joint function. A titanium-based 3D-printed strut-type prosthesis, featured with excellent biocompatibility and osseointegration ability, was developed for this bone defect in our institution. The goal of this study is to comparatively analyze the biomechanical performance of reconstruction methods aimed at the identification of better operative strategy.Four different 3D finite element models were created. Model #1: Normal femur; Model #2: Femur with tumorous cavity bone defects in the distal femur; Model #3: Cavity bone defects reconstructed by cement packing combined with subchondral bone grafting and extra fixation; Model #4: Cavity bone defects reconstructed by 3D-printed strut-type prosthesis combined with subchondral bone grafting. The femoral muscle multiple forces were applied to analyze the mechanical difference among these models by finite element analysis.Optimal stress and displacement distribution were observed in the normal femur. Both reconstruction methods could provide good initial stability and mechanical support. Stress distributed unevenly on the femur repaired by cement packing combined with subchondral bone grafting and extra fixation, and obvious stress concentration was found around the articular surface of this femur. However, the femur repaired by 3D-printed strut-type prosthetic reconstruction showed better performance both in displacement and stress distribution, particularly in terms of the protection of articular surface and subchondral bone.3D-printed strut-type prosthesis is outstanding in precise shape matching and better osseointegration. Compared to cement packing and extra fixation, it can provide the almost same support and fixation stiffness, but better biomechanical performance and protection of subchondral bone and articular cartilage. Therefore, 3D-printed strut-type prosthetic reconstruction combined with subchondral bone grafting may be evaluated as an alternative for the treatment of GCTBs in distal femur.© 2022. The Author(s).