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Introduction: Clinical studies have indicated reduced reliance on blocking screws with the introduction of polyaxial locking nails, yet the biomechanical superiority of polyaxial locking over blocking screws remains unverified, specifically for distal dia-metaphyseal femur fractures., Hypothesis: We hypothesized that the combination of multiaxial locking using three screws and parallel locking reinforced by two blocking screws would result in superior outcomes compared to utilizing only parallel locking with two screws and one blocking screw., Materials and Methods: Third-generation custom-made femur models representing AO/OTA 32 A1.2 dia-metaphyseal comminuted oblique fractures were divided into four groups (n=10/group). Group A employed distal fixation with three 4.5-mm polyaxial screws. Group B used two parallel locking screws and two blocking screws, Group C used two parallel locking screws and one blocking screw, and Group D used only two parallel screws. Specimens underwent axial and torsional load testing to assess fatigue strength, ultimate strength, axial stiffness (N/mm), torsional stiffness (N/mm/deg), axial load to failure (N), torsional load to failure (N/mm), coronal and sagittal angulations, and fracture site collapse., Results: Group C exhibited statistically superior torsional stiffness compared to Groups B and D (p=0.039 and p=0.034, respectively). Axial load to failure was highest in Group B and lowest in Group D (p=0.032). Group C demonstrated the highest torsional strength, while Group B exhibited the lowest (p=0.006). Coronal displacement was greatest in Group B, while Group A showed the highest resistance (p=0.009). Group A demonstrated the greatest resistance to fracture site collapse, with the weakest specimens observed in Groups B and C (p=0.01)., Discussion: The performance of a single laterally positioned blocking screw is comparable to using two blocking screws. Medial positioning of a second blocking screw is unnecessary for stability enhancement. Multiaxial locking prevents fracture site collapse and coronal plane angulation more effectively than other methods. Multiaxial locking and/or parallel screws with a single laterally positioned blocking screw provide superior stiffness and stability for treating unstable dia-metaphyseal distal femoral fractures., Level of Evidence: N/A., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)