There has been no scientific mechanical assessment demonstrating the optimal fixation technique in multifragmentary fractures of the distal humeral shaft. The purpose of the present study was to compare the biomechanical performance of 5 fixation constructs as used in minimally invasive plating osteosynthesis (MIPO) for distal humeral shaft fractures. Three-dimensional (3D) humerus model with 20mm distal humeral shaft fracture gap simulating multifragmentary fracture was created from computed tomography data and virtually fixed by 5 fixation techniques as MIPO, i.e., anterior narrow dynamic compression plate (DCP), anterior narrow locking compression plate (LCP), anterior reversed proximal humeral internal locking system (R-PHILOS), extra-articular distal humerus locking compression plate (LCP-EADH), and anteromedial LCP. All constructs were biomechanically tested under 6 loading conditions by means of finite element analysis, i.e., 250-N axial compression, 7.5-Nm internal rotation, 7.5-Nm external rotation, 10-Nm posterior bending, 10-Nm valgus rotation, and 10-Nm varus rotation. In addition, A 3D model of each construct was fabricated as 3D printed models. Fixations were applied to the 3D printing model which were later mechanically tested to validate the FE results. EQV stress exhibited on anterior narrow LCP and anterior R-PHILOS were comparable which were lower than other constructs under axial compression and valgus-varus bending. Anterior R-PHILOS produced lower EQV stress than other constructs under internal-external rotation and posterior bending. On the whole, R-PHILOS demonstrated a comparable fracture displacement to those LCP with anterior or anteromedial approaches, that achieved the lowest displacement values. In addition, the experimental mechanical test values shared a correlation with the FE model results. Overall, the anterior R-PHILOS was considered as a potential candidate for multifragmentary distal humeral shaft fractures. It demonstrated efficacious biomechanical performance in terms of implant stress and distal fragment displacement.