The aim of this randomized controlled trial was to measure and compare six-degree-of-freedom (6-DOF) knee joint motion of three total knee arthroplasty (TKA) implant designs across a range of daily activities. Seventy-five TKA patients were recruited to this study and randomly assigned a posterior-stabilized (PS), cruciate-retaining (CR), or medial-stabilized (MS) implant. Six months after surgery, patients performed five activities of daily living:​ level walking, step-up, step-down, sit-to-stand, and stand-to-sit. Mobile biplane X-ray imaging was used to measure 6-DOF knee kinematics and the center of rotation of the knee in the transverse plane for each activity. Mean 6-DOF knee kinematics were consistently similar for PS and CR, whereas MS was more externally rotated and abducted, and lateral shift was lower across all activities. Peak-to-peak anterior drawer for MS was also significantly lower during walking, step-up, and step-down (p < 0.017). The center of rotation of the knee in the transverse plane was located on the medial side for MS, whereas PS and CR rotated about the lateral compartment or close to the tibial origin. The kinematic function of MS was more similar to that of the healthy knee than PS and CR based on reduced paradoxical anterior translation at low flexion angles and a transverse center of rotation located in the medial compartment. Overall, 6-DOF knee joint motion for PS and CR were similar across all daily activities, whereas that measured for MS was appreciably different. The kinematic patterns observed for MS reflects a highly conforming medial articulation in the MS design.