Abstract The implantation of total knee replacements is an effective treatment for advanced degenerative knee joint diseases. Implant positioning relative to the bones affects the loads occurring in the artificial joint, joint stability, and postoperative functionality. Variance in implant positioning during the surgical implantation of a total knee replacement cannot be entirely ruled out. By simulating implant malpositioning in an experimental setting, particularly critical cases of malalignment can be identified, from which guidelines for orthopedic surgeons can be derived. The AMTI VIVO™ six degree of freedom joint simulator allows reproducible preclinical testing of joint endoprostheses under specific kinematic and loading conditions. It features a virtual ligament model that defines up to 100 ligament fibers between the articulating components. This paper presents a method to investigate the effect of different implant positions on the biomechanics of the knee after total knee arthroplasty. For this, the VIVO joint simulator requires no modification of the physical setup by moving virtual ligament insertion points relative to the bone. As a proof of concept, exemplary shifts and rotations of the femoral and tibial implant components are performed, and dynamic results are compared to a musculoskeletal multibody digital twin and findings from the literature.