Accurate knowledge of in vivo ankle joint complex (AJC) biomechanics is critical for understanding AJC disease states and for improvement of surgical treatments. This study investigated 6 degrees-of-freedom (DOF) in vivo kinematics of the human AJC using a combined dual-orthogonal fluoroscopic and magnetic resonance imaging (MRI) technique. Five healthy ankles of living subjects were studied during three in vivo activities of the foot, including maximum plantarflexion and dorsiflexion, maximum supination and pronation, and three weight-bearing positions in simulated stance phases of walking. A three-dimensional (3D) computer model of the AJC (including tibia, fibula, talus, and calcaneus) was constructed using 3D MR images of the foot. The in vivo AJC position at each selected position of the foot was captured using two orthogonally positioned fluoroscopes. In vivo AJC motion could then be reproduced by coupling the orthogonal images with the 3D AJC model in a virtual dual-orthogonal fluoroscopic system. From maximum dorsiflexion to plantarflexion, the arc of motion of the talocrural joint (47.5 AE 2.28) was significantly larger than that of the subtalar joint (3.1 AE 6.88). Both joints showed similar degrees of internalexternal and inversion-eversion rotation. From maximum supination to pronation, all rotations and translations of the subtalar joint were significantly larger than those of the talocrural joint. From heel strike to midstance, the plantarflexion contribution from the talocrural joint (9.1 AE 5.38) was significantly larger than that of the subtalar joint (À0.9 AE 1.28). From midstance to toe off, internal rotation and inversion of the subtalar joint (12.3 AE 8.38 and À10.7 AE 3.88, respectively) were significantly larger than those of the talocrural joint (À1.6 AE 5.98 and À1.7 AE 2.78). Strong kinematic coupling between the talocrural and subtalar joints was observed during in vivo AJC activities. The contribution of the talocrural joint to active dorsi-plantarflexion was higher than that of the subtalar joint, whereas the contribution of the subtalar joint to active supination-pronation was higher than that of the talocrural joint. In addition, the talocrural joint demonstrated larger motion during the early part of stance phase while the subtalar joint contributes more motion during the later part of stance phase. The results add quantitative data to an in vivo database of normals that can be used in clinical diagnosis, treatment, and evaluation of the AJC after injuries. ß