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The purpose of this study was to examine the influences of caster orientations and driving speeds on the reverse directional stability of electric-powered wheelchairs. An experiment was set up to record wheelchair trajectories and ground reaction forces/moments for the front caster wheels and rear wheels when a wheelchair initiates reverse motions at six initial caster orientations and three desired driving speeds. A kinematic model as well as a dynamic model were developed to simulate the wheelchair motion and conduct a parametric study of different factors on wheelchair reverse directional stability. The experimental and simulation results show agreement, both of which indicate that different caster orientations at the start of reverse driving introduce disturbances and the faster the intended speed, the less deviation of the wheelchair from its desired heading. The center of gravity (CG) was also found to be a dominant influence on the reverse directional stability of power wheelchairs.