OBJECTIVE Malposition of the femoral Less Invasive Stabilization System (LISS) plate may alter its biomechanical behavior. This study compares the mechanical stability of "correctly" affixed LISS plates matching the slope of the lateral femoral condyle to "incorrectly" placed LISS plates fixed in external rotation relative to the distal femur. METHODS A fracture gap model was created to simulate a comminuted supracondylar femur fracture (AO/OTA33-A3). Fixation was achieved using two different plate positions: the LISS plate was either placed "correctly" by internally rotating the plate to match the slope of the lateral femoral condyle, or "incorrectly" by externally rotating the plate relative to the distal femur. Following fixation, the constructs were loaded in axial, torsional, and cyclical axial modes in a material testing machine. MAIN OUTCOME MEASUREMENT Stiffness in axial and torsional loading; total deformation and irreversible (plastic) deformation in cyclical axial loading. RESULTS The mean axial stiffness for the correctly placed LISS constructs was 21.5% greater than the externally rotated LISS constructs (62.7 N/mm vs. 49.3 N/mm; P = 0.0007). No significant difference was found in torsional stiffness between the two groups. Cyclical axial loading caused significantly less (P < 0.0001) plastic deformation in the correct group (0.6 mm) compared with externally rotated group (1.3 mm). All the constructs in the incorrect group failed, where failure was defined as a complete closure of the medial fracture gap, prior to completion of the test cycles. CONCLUSION Correct positioning of the LISS plate for fixation of distal femur fractures results in improved mechanical stability as reflected by an increased stiffness in axial loading and decreased plastic deformation at the bone-screw interface.