The assistive robot system adaptive head motion control for user-friendly support (AMiCUS) has been developed to increase the autonomy of motion impaired people. The six degrees of freedom robot arm with gripper is controlled with head motion and head gestures only, so especially tetraplegics benefit from collaboration with AMiCUS. In this paper, a usability study with a total number of 30 subjects was conducted to validate the AMiCUS interaction technology and design. 24 able-bodied subjects of demographically diverse groups and 6 tetraplegics participated in this paper. All subjects performed different pick and place tasks by controlling AMiCUS. The evaluation of the interaction design was carried out subjectively with a questionnaire as well as objectively by measurement of time, completion rate, and number of trials for correct head gesture performance. The influence of several factors like age, sex, motion impairment, and previous experience on head motion-based human-robot interaction was analyzed. The interaction design has been proven successful in laboratory environment and assessed overall positive by the subjects. The results of the presented paper confirm the usability of the assistive robot AMiCUS. AMiCUS has the potential to benefit tetraplegics by improving their independence in activities of daily living and adapted workplaces.