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The transepicondylar axis (TEA) is often used as a surrogate for the flexion-extension axis, ie, the axis around which the tibia moves in space, because of a belief that both axes lie perpendicular to the mechanical axis. However, studies suggest the cylindrical axis (CA), defined as a line equidistant from contact points on the medial and lateral condylar surfaces from 10(o) to 120(o) flexion, more closely approximates the axis around which the tibia moves in space.We examined the TEA and CA angles relative to mechanical axes to determine whether one more consistently and closely approximates the surgical goal of orthogonality to the mechanical axis.Three-dimensional (3-D) models were reconstructed from CT scans of five cadaver limbs. Three observers repeated three measurement sets to locate the TEA, CA, and femoral mechanical and tibial mechanical axes. Angles of the TEA and CA relative to the mechanical axes were calculated in two-dimensions (2-D) and as 3-D projections and compared for differences in magnitude and variance.Angles between CA and the mechanical axes were closer to 90° than the TEA in 2-D (92° versus 94° for the femur, 93° versus 94° for the tibia) and 3-D (88° versus 87° for the femur, 88° versus 86° for the tibia). Variance of the TEA was higher than the CA in 2-D.The CA forms angles more orthogonal to the mechanical axes of the thigh and leg than the TEA.Although we found a consistently greater deviation of the TEA from the mechanical axis than the CA with small differences, future studies will need to determine whether these differences are biomechanically or clinically important.