BackgroundManagement of proximal humerus fractures is challenging, especially in elderly. Locking plating is a common surgical treatment option. The Proximal Humerus Internal Locking System (plate-A) has shown to lower complication rates compared to conventional plates, but is associated with impingement risk, which could be avoided using Peri-articular Proximal Humerus Plate (plate-B). Nevertheless, biomechanical performance and optimal screw configuration of plate-B is unknown. The aim of this study was to evaluate different screw configurations of plate-B and compare with plate-A using finite element analyses. MethodsTwenty-six proximal humerus models were osteotomised to create unstable three-part fractures, fixed with either of the two plates, and tested under three anatomical loading conditions using a previous established and validated finite element simulation framework. Various clinically relevant screw configurations were investigated for both plates and compared based on the predicted peri-implant bone strain, being a validated surrogate of cyclic cut-out failure. FindingsBesides increasing the number of screws, the placement of the posterior screws in combination with the calcar screw in the plate-B significantly decreased the predicted failure risk. Generally, plate-A had a lower predicted failure risk than plate-B. InterpretationThe posterior and calcar screws may be prioritized in plate-B. Compared to plate-A, the more distal positioning, less purchase in the posterior aspect and a smaller screw spread due to not fitting of the most distal calcar screw in most investigated subjects led to a significantly higher predicted failure risk for most plate-B configurations. The findings of the simulations study require clinical corroboration.