To examine the effects of locked distal screws in retrograde nails used in unstable osteopenic distal femur fractures. Biomechanical testing of paired human cadaveric femurs. Seven matched pairs of embalmed, moderately osteopenic cadaver femurs were instrumented with 12-mm intramedullary nails in a statically locked, retrograde fashion. One femur of each pair had locked distal screws and the other femur had unlocked distal screws. A 2.5-cm gap of bone was cut nine centimeters from the distal condyles to simulate an unstable fracture. The locked distal screw nails were compared to unlocked distal screw nails for collapse of the fracture gap, medial-lateral and anterior-posterior translation of the nail within the fracture site, and fracture angulation. The femurs were axially loaded, cycled, and then loaded to failure. Motion at the fracture site with axial cyclic loading and site of failure when loaded to failure. After cycling, both locked distal screw and unlocked distal screw nails demonstrated several millimeters medial and anterior translation within the fracture site and approximately 1 mm collapse of the fracture gap. Although no statistically significant differences were found, the locked distal screw nails had less anterior and medial translation, angulation, and collapse of the fracture gap after cycling. Loads to failure were similar for both locked distal screw and unlocked distal screw nails. It was noted that proximal femur failure occurred at the level of the proximal screw hole in the nail at the subtrochanteric level in 7 (4 locked distal screws and 3 unlocked distal screw groups) of the 14 samples. Four other samples failed through the intertrochanteric region (2 locked distal screw and 2 unlocked distal screw groups) and the remainder within the distal fragment by fracture of the femur along the medial cortex. Although most differences in fixation stability were not significant, the locked distal screw nails exhibited less fracture collapse and anterior and medial translation of the nail at the fracture site than the unlocked distal screw nails. The degree of varus angulation after cyclic loading was also less for the locked distal screw nails. The length of the nail chosen should avoid having proximal locking screws distal to the lesser trochanter, thus averting proximal femur stress risers and fractures.