Objectives: To compare the initial stability of the genucephalic (GSH) intramedullary nail and the 95-degree condylar compression screw and side plate (DCS) for distal femur fractures. Design: Human cadaveric biomechanical study. Participants: Twelve matched pairs of fresh frozen human cadaveric femurs. Intervention: Genucephalic intramedullary nail device (Smith and Nephew Richards, Memphis, TN, U.S.A.) and the 95-degree DCS device (Synthes USA, Paoli. PA, U.S.A.) were compared. Grouped or dispersed screw constructs were tested for each fracture fixation system with progressively more severe simulated fracture patterns. Main Outcome Measurement: Axial and torsional stiffness values. Results: The DCS plate with the dispersed screw configuration had the greatest torsional stiffness (p < 0.0011). The GSH nail with the grouped screw configuration absorbed more energy (work) during axial loading compared with the plate constructs (p < 0.0007). There were no significant differences in axial or torsional stiffness within treatment groups for fracture patterns of increasing severity. Conclusions: Based on the authors' results, the selection of a GSH nail or a DCS plate should not be determined by the severity of the fracture. If a DCS plate construct is selected, the authors recommend a dispersed screw configuration, including the most proximal hole in the plate, to provide superior stiffness in torsional loading and equal stiffness in axial loading when compared with the GSH nail constructs. If a GSH nail is selected, the authors recommend a grouped screw configuration, which absorbed more energy during axial loading compared with the DCS plate constructs and the nail with the dispersed screw configuration.