This study presents a new method to estimate 3-D linear accelerations at tibial and femoral functional coordinate systems. The method combines the use of 3-D accelerometers, 3-D gyroscopes and reflective markers rigidly fixed on an exoskeleton and, a functional postural calibration method. Marker positions were tracked by a six-camera optoelectronic system (VICON 460, Oxford Metrics). The purpose of this study was to determine if this method could discriminate between medial osteoarthritic and asymptomatic knees during gait. Nine patients with osteoarthritic knees and nine asymptomatic control subjects were included in this study. Eighteen parameters representing maximal, minimal, and range of acceleration values were extracted during the loading and preswing to mid-swing phase periods, and were compared in both groups. Results show good discriminative capacity of the new method. Eight parameters were significantly different between both groups. The proposed method has the potential to be used in comprehending and monitoring gait strategy in patients with osteoarthritic knee.