Introduction: The indications for intramedullary nail fixation of fractures of the femoral shaft have been greatly expanded by techniques of interlocking nailing. However, distal locking screw fixation remains the most technically demanding and problematic portion of the procedure and maybe responsible for as much as one-half of the exposure of the surgeon’s hands to radiation during the procedure. Objective: This biomechanical study was undertaken to compare the stability of using one distal locking cross screw versus two cross screws in femoral fractures fixed with intramedullary nailing (IMN) system. Materials: A composite model made from a stainless steel IMN (12 mm × 1 mm) was connected to a load cell (Instron machine). Axial forces upto 2 kN (3 times body weight) was applied or until a maximum displacement of 1 mm was reached. The distal locking end of the intramedullary nail was secured with stainless steel cylinders of different dimensions 50 mm × 5 mm, 75 mm × 5 mm and 100 mm × 3 mm to represent the proximal femoral diaphysis, diaphyseo-metaphyseal junction and distal femoral metaphyseal respectively. The distal locking end of the intramedullary nail was attached to the cylinder with a dedicated single or two rods (5 mm diameter), made from stainless steel, to represent the distal locking cross screw. Results: In the 50 mm cylinder, the mean stiffness (±standard deviation) of the system using either single or two screws were similar i.e. 3298 ± 144 N/mm. But in the 75 mm and 100 mm cylinders, the mean stiffness of the fracture model with two distal locking cross screws fixation was 2.059 ± 96 N/mm and 0.816 ± 122 N/mm and with single distal locking cross screw fixation were 0.643 ± 142 N/mm and 0.289 ± 88 N/mm respectively. Conclusion: Single distal locking cross screw fixation provide poorer fracture stability compared to two distal locking cross screws when used to fix distal femoral metaphyseal fractures.