Prophylactic cerclage cables are often placed intraoperatively about a fracture to prevent propagation. However, biomechanical data supporting optimal cable placement location are lacking. The objective of this study was to evaluate the impact of prophylactic cerclage placement location on the propagation of femoral shaft fractures. The diaphysis of 14 fresh-frozen cadaveric femora were included. Volumetric bone mineral density in the femoral shaft was obtained from quantitative computed tomography scans. For each specimen, a 5-mm longitudinal fracture was created proximally to simulate a pre-existing fracture. After reaming of the femoral canal, a 3 degrees tapered wedge was advanced with an MTS machine at 0.2 mm/s until failure. The tests were conducted with a CoCr cable placed at varying distances (5 mm, 10 mm, 15 mm, 20 mm, and cableless) from the distal tip of the initial fracture. A compression loadcell was used to measure the cable tension during the tests. The axial force, displacement, and cable tension were monitored for comparison between groups. In the cableless group, the mean force needed to propagate the fracture was 1017.8 ± 450.3 N. With the addition of a cable at 5 mm below the fracture, the failure force nearly doubled to 1970.4 ± 801.1 N (P < 0.001). This also led to significant increases in stiffness (P = 0.006) and total work (P = 0.001) when compared with the control group. By contrast, in the 15 and 20 mm groups, there were no significant changes in the failure force, stiffness, and total work as compared with the control group (P > 0.05). Propagation of femoral shaft fracture was effectively resisted when a prophylactic cable was placed within 5 mm from the initial fracture, whereas cables placed more than 10 mm below the initial fracture were not effective in preventing fracture propagation.