Introduction. Non-union is debilitating, costly and affects 2–8% of intramedullary fixed fractures. Clinical data suggest that percutaneous interfragmentary screws offer a less invasive alternative to exchange nailing. This study aimed to assess their efficiency with biomechanical analyses. Materials and Methods. A tibia was prepared for finite element analysis by creating a fracture of AO classification 42A2b, prior to reaming and insertion of an intramedullary nail. A callus was modelled as granulation tissue and gait loads were applied. The model was validated against published data and with sensitivity studies. The effects of weightbearing, fracture gap and angle, percutaneous screws and exchange nailing were compared through quantification of interfragmentary motion and strain, with the latter used to gauge healing performance via mechano-regulation theory. Results. Axial interfragmentary motion increased with increasing weightbearing, however, shear decreased at 25–50% weightbearing, leading to superior healing performance. Fracture gap had minimal effect on axial motion, but larger gaps gave greater shear, compromising healing. Elevated fracture obliquity culminated in more shear and inferior healing. Exchange nailing reduced axial motion by ∼30%, but had little effect on shear. Conversely, percutaneous screws had negligible effect on axial motion, but reduced shear by ∼15%, with three screws having a similar net effect on healing as exchange nailing from 10 to 11mm. Conclusions. This study provides new insight into fracture healing biomechanics and discovered that partial weightbearing, less oblique fractures and percutaneous screws all reduce shear, enhancing healing