Abstract Objectives The aim of this study was to measure and compare the stiffness and cyclic fatigue of two plate-bone model constructs, with either two or three locking screws per fragment, under cyclic compression. Methods A 10-hole 3.5 mm stainless steel locking compression plate (LCP) was fixed 1 mm from a synthetic bone model in which the fracture gap was 47 mm. Two groups of 10 constructs, prepared with either two or three bicortical locking screws placed at the extremities of each fragment, were tested in a load-controlled compression test until failure. Results The three-screw constructs were stiffer than the two-screw constructs (196.75 ± 50.48 N/mm and 102.43 ± 22.93 N/mm, respectively) and the actuator displacements of the two-screw constructs were higher (18.02 ± 1.07 mm) than those of the three-screw constructs (14.48 ± 2.25 mm). The number of cycles to failure of the two-screw constructs was significantly lower (38,337.50 ± 2,196.98) than the that of the three-screw constructs (44,224.00 ± 1,515.24). Load at irreversible deformation was significantly lower in the two-screw constructs (140.93 ± 13.39 N) than in the three-screw constructs (184.27 ± 13.17 N). All constructs failed by plate bending at the gap between the two cylinders. Clinical Significance Omission of the third innermost locking screw during bridging osteosynthesis subjected to compression forces led to a 13.3% reduction in the number of cycles to failure and a 23.5% reduction of the load withstood by the plate before plastic deformation occurred.