Purpose The purpose of this study was to compare the biomechanical stability generated when utilizing increasing sizes of titanium (Ti) flexible nails for fixation of simulated comminuted femur fractures. Methods Five synthetic adolescent-sized femur models were reamed to create a 9-mm canal. A 2-cm section was removed in the mid-diaphysis to simulate comminution. Each femur was first stabilized with bilateral, retrograde 3.0-mm titanium elastic nails. Femurs were tested in axial rotation and axial compression. The constructs were removed, and femurs were re-nailed with 3.5-mm nails. Identical testing was conducted. These nails were then removed, and femurs were re-nailed with 4.0-mm nails. This provided data on ''canal fill'' representing 67, 78 and 89% of the reamed canal diameter. Data for axial rotation (degrees) and failure load (N) required to produce 5 mm of fracture shortening were analyzed with a one-way ANOVA (P \ 0.05) and a Tukey's post-hoc test for multiple comparisons. Results For axial rotation, there were statistically significant improvements in rotational control for each increase in nail size. For axial stability, each increase in nail size resulted in increased axial failure loads to 5 mm, although these data were not statistically different. A specific comparison between 3.0-and 3.5-mm nails for compressive stability found significantly greater stability afforded by using 3.5-mm nails. Conclusions Data from this study demonstrate that increasing the amount of canal fill provides significant improvements in rotational control. The largest improvement was seen when increasing from 3.0-to 3.5-mm nails. While increasing the nail size from 3.5 to 4.0 mm again provided greater stability, larger nails may be more difficult to insert. Thus, increasing the nail size for femoral fracture fixation should be considered after measuring the diameter of the canal and evaluating the potential difficulty of insertion as well as specific demands of the fracture pattern.