For evaluating the impact of knee surgery, cadaveric knee simulators are commonly applied. However, most of the knee simulators are based on the Oxford type as originally described by Zavatsky (Zavatsky, J. of Biomechanics, 1997). These simulators mainly focus on the squatting motion. Although a wide range of flexion angles can be examined while performing this motion, the significance for activities of daily living is limited. To that extent a new knee simulator has recently been developed at Ghent University. In this simulator, the ankle motion is dynamically controlled in the sagittal plane; both in the proximal/distal direction and the anterior/posterior direction. As a result, this simulator allows simulating random motion patterns, e.g. cycling, stair ascent and descent, … The ankle translation is unrestrained in the medial/lateral direction. In addition, all rotational degrees of freedom are unrestrained at the ankle, resulting in four degrees of freedom at the ankle. The hip adds one rotational degree of freedom being the rotation in the sagittal plane. This leaves 5 degrees of freedom (DOF) to the knee; the sixth being flexion/extension that is controlled by the actuators at the ankle. During the simulation of different motion patterns, the quadriceps and hamstring force are actively controlled to mimic realistic conditions obtained through musculoskeletal simulations. In this study, five cadaveric experiments have been performed on the simulator. While mounting the cadaveric specimens in the test rig, the initial alignment remains crucial. Whilst the rig leaves 5 DOF to the knee, it is important to restore the anatomical position of the hip and ankle. To minimize the impact of the mounting procedure, cadaver specific 3D printed guides are used to assure the alignment of the cadaver in the test rig. As a result, the kinematics are more likely to represent physiological conditions. These kinematics have been evaluated in accordance to the methodology described by Grood&Suntay (Grood & Suntay, Transactions of the ASME, 1983). Therefore, a CT scan of the examined knee is combined with motion tracking data from rigidly attached markers on both the femur and the tibia. The cadaveric knees have been subjected to a variety of motion patterns, i.e. squatting and cycling. The squatting experiments provide evidence that the knee simulator creates adequate boundary conditions as the kinematic patterns coincide with literature reportings. The cycling experiments however significantly differ from the squatting patterns. Most noteworthy is the difference in terms of internal/external rotation for these native knees (Figure 1). This internal/external rotations is highly fluctuating from flexion to extension. This is understood as the quadriceps force is not constant during the extension phase, representing physiological conditions. Conclusion. Significant difference in knee kinematics between squatting and cycling indicates the importance of testing a variety of conditions. Furthermore, this reveals the need to study clinically relevant motion patterns, selected from patient reported outcomes