We examined the reliability of the anteroposterior and posterior condylar axes for determining rotational alignment of the femoral component in total knee arthroplasty (TKA). A computed tomography scan was taken at the level of the femoral epicondyle in 84 knees (27 varus knees with medial femorotibial arthritis (FT-OA) in 26 patients, 17 knees with patellofemoral arthritis in 14 patients, and 40 normal knees in 40 volunteers). On the image, an anteroposterior axis, a line perpendicular to the anteroposterior axis, an epicondylar axis and a posterior condylar axis were drawn, and the relationship between the three axes was assessed. The mean values for the 84 knees were evaluated, and the posterior condylar axis was 6.0 degrees +/- 2.4 degrees internally rotated relative to the epicondylar axis, while the line perpendicular to the anteroposterior axis was 1.4 degrees +/- 3.3 degrees internally rotated relative to the epicondylar axis. The internal rotation angle of the posterior condylar axis relative to the epicondylar axis was 6.2 degrees +/- 1.9 degrees in the knees with medial femorotibial arthritis, 6.4 degrees +/- 2.4 degrees in the knees with patellofemoral arthritis, and 5.8 degrees +/- 2.7 degrees in the normal knees, showing consistent values in normal and osteoarthritic knees. The internal rotation angle of the line perpendicular to the anteroposterior axis relative to the epicondylar axis was 0.1 degrees +/- 3.3 degrees, 1.3 degrees +/- 3. 3 degrees, and 2.3 degrees +/- 3.1 degrees in the three groups, respectively (i.e., there were significant differences between the medial FT-OA knees and the normal knees). The results demonstrated that the anteroposterior axis was rotated externally to a significant degree in medial FT-OA knees and was less reliable than the posterior condylar axis for use in alignment for TKA on medial FT-OA knees.