Background Construct stiffness affects healing of bones fixed with locking plates. However, variable construct stiffness reported in the literature may be attributable to differing test configurations and direct comparisons may clarify these differences. Questions/purposes We therefore asked whether different distal femur locking plate systems and constructs will lead to different (1) axial and rotational stiffness and (2) fatigue under cyclic loading. Methods We investigated four plate systems for distal femur fixation (AxSOS, LCP, PERI-LOC, POLYAX) of differing designs and materials using bone substitutes in a distal femur fracture model (OTA/AO 33-A3). We created six constructs of each of the four plating systems. Stiffness under static and cyclic loading and fatigue under cyclic loading were measured.