Recent modifications in total knee prosthesis design theoretically better accommodate the anatomy of the female femur and thereby have the theoretical potential to improve clinical results in TKA by more accurately restoring femoral posterior condylar offset, reducing femoral notching, reducing femoral component flexion, and reducing component overhang. First, we radiographically evaluated whether a contemporary unisex prosthesis would accommodate female anatomy equally as well as male anatomy. Next, we radiographically evaluated female knees in which a gender-specific prosthesis was used. Pre- and postoperative radiographs of 122 knees (42 female unisex, 41 male unisex, 39 female gender-specific) were reviewed. In the unisex groups, there were no differences in femoral notching or femoral component flexion. Posterior femoral offset increased in both groups. However, femoral component overhang was worse in female knees (17%) than in male knees (0%). In the gender-specific female group, the incidence of component overhang was similar to that in the unisex female group. Unisex femoral components of this specific design do not equally match the native anatomy male and female knees. In some women, a compromise was required in sizing.