Abstract: This study is aimed at developing a methodology to assess and quantify the human limb motions and interactions with the exoskeleton in relation to alignment. Three different basic and common upper arm joint movements and their interaction with a joint-based exoskeleton are considered: shoulder vertical and horizontal abduction–adduction, and elbow flexion–extension. The exoskeleton and the human model are aligned to the respective joints inside a Musculoskeletal Modeling software. Within the range of motion, the linear and angular displacement errors were analyzed, and the effect of those errors on the length of the associated tendons was studied. Results have shown a noticeable variation of the muscle-tendon lengths up to 65.7 mm and a change in the pattern on different muscle groups of the shoulder. Similarly, about 4 mm muscle-tendon length changes observed particularly at the elbow anconeus muscle-tendon. These changes of length could cause unwanted stresses at the joints, specially for people with disabilities due to stroke that might not have the flexibility to accommodate those extra pose variations imposed by the exoskeleton.