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A noninvasive method for determining the instantaneous axis of rotation (IAOR) of the foot and ankle during human ambulation has been developed. The algorithm uses three-dimensional (3-D) external marker trajectories to describe the IAOR of the calcaneus with respect to the tibia. Multiple optimization techniques were used to fit a plane and a sphere to the marker trajectories, with the constraint that the center of the sphere lies on the plane. The IAOR was defined perpendicular to the plane and passed through the center of the sphere. The results from validation procedures have demonstrated the applicability of the method. Experimental IAOR data acquired from normal adult subjects indicated the ability to track the IAOR during gait. This self-determining system for locating a patient's foot and ankle IAOR during gait may benefit rehabilitation applications in pedorthic and prosthetic design, surgical and nonsurgical treatment, and rehabilitative approaches to suprasegmental functional accommodation.