Mal-rotation of the components in total knee arthorplasty (TKA) is a major cause of postoperative complications, with an increased propensity for implant loosening or wear leading to revision. A musculoskeletal multi-body dynamics model was used to perform a parametric study of the effects of the rotational mal-alignments in TKA on the knee loading under a simulated walking gait. The knee contact forces were found to be more sensitive to variations in the varus-valgus rotation of both the tibial and the femoral components and the internal-external rotation of the femoral component in TKA. The varus-valgus mal-rotation of the tibial or femoral component and the internal-external mal-rotation of the femoral component with a 5˚variation were found to affect the peak medial contact force by 17.8-53.1%, the peak lateral contact force by 35.0-88.4% and the peak total contact force by 5.2-18.7%. Our findings support the clinical observations that a greater than 3˚internal mal-rotation of the femoral component may lead to unsatisfactory pain levels and a greater than 3˚varus mal-rotation of the tibial component may lead to medial bone collapse. These findings determined the quantitative effects of the mal-rotation of the components in TKA on the contact load. The effect of such malrotation of the components of TKA on the kinematics would be further addressed in future studies. Keywords: total knee arthroplasty; mal-rotation; multi-body dynamics; musculoskeletal model; contact forceThe fundamental objectives of total knee arthroplasty (TKA) are to restore normal knee joint function and to relieve pain. However, the failure in TKA resulting from clinical error and mal-alignment of the components limits the long-term survivorship of such prostheses. Dalury et al. 1 retrospectively identified 820 consecutive revision TKAs and found that malposition/mal-alignment was the seventh highest reason for revision. However, mal-position/mal-alignment also affects joint loading, component loosening and wear so that it may have a much larger effect on revision. For example, mal-rotation of the components in TKA may result in overload in the medial or lateral condyle, bone damage and bone cement crack initiation, severe wear of the polyethylene component, component loosening, and ultimately revision surgery. 2,3 In contrast, good alignment measured against the neutral position (referenced to the mechanical axis to within 2˚) after TKA leads to faster rehabilitation and better function. 4 In previous clinical studies, 5 the issue of malrotation was the most frequently discussed complication in TKA. Mal-rotation of a measurable degree has been found in approximately 10-30% of patients with TKA, depending on the surgical technique and the anatomical landmarks used. 5 Even in the hands of experienced surgeons, overall coronal mal-alignment (> AE 3˚from neutral) existed in approximately 28% of the patients. 6 Despite the improvements in surgical instruments and techniques as well as implant designs, a large percentage of the cause...