Individuals who propel wheelchairs have a high prevalence of upper extremity injuries (i.e., carpal tunnel syndrome, elbow/shoulder tendonitis, impingement syndrome). Musculoskeletal injuries can result from overuse or incorrect use of manual wheelchairs, and can hinder rehabilitation efforts. To better understand the mechanisms of upper extremity injuries, this study investigates the motion of the wrist during wheelchair propulsion. This study also examines changes in the variables that occur with fatiguing wheelchair propulsion to determine how the time parameters of wheelchair propulsion and the state of fatigue influence the risk of injury. A two dimensional (2-D) analysis of wrist movement during the wheelchair stroke was performed. Twenty subjects propelled a wheelchair handrim on a motor-driven treadmill at two different velocities (50, 70 m/min). The results of this study were as follows; The difference in time parameters of wheelchair propulsion (cadence, cycle time, push time, recovery time, and PSP ratio) at two different velocities was statistically significant. The wrist kinematic characteristics had statistically significant differences at two different velocities, but wrist radial deviation and elbow flexion/extension had no statistically significant differences. There were statistically significant differences in relation to fatigue in the time parameter of wheelchair propulsion (70 m/min) between initial 1 minute and final 1 minute. The wrist kinematic characteristics between the initial 1 minute and final 1 minute in relation to fatigue had statistically significant differences but the wrist flexion-extension (50 m/min) had no statistically significant differences. According to the results, the risk of musculoskeletal injuries is increased by fatigue from wheelchair propulsion. To prevent musculoskeletal injuries, wheelchair users should train in a muscle endurance program and consider wearing a splinting/grove. Moreover, wheelchair users need education on propulsion posture, suitable joint position, and proper recovery patterns of propulsion.