Robotic exoskeletons can be used to study and treat patients with neurological impairments. They can guide and support the human limb over a large range of motion, which requires that the movement trajectory of the exoskeleton coincide with the one of the human arm. This is straightforward to achieve for rather simple joints like the elbow, but very challenging for complex joints like the human shoulder, which is comprised by several bones and can exhibit a movement with multiple rotational and translational degrees of freedom. Thus, several research groups have developed different shoulder actuation mechanism. However, there are no experimental studies that directly compare the comfort of two different shoulder actuation mechanisms. In this study, the comfort and the naturalness of the new shoulder actuation mechanism of the ARMin III exoskeleton are compared to a ball-and-socket-type shoulder actuation. The study was conducted in 20 healthy subjects using questionnaires and 3D-motion records to assess comfort and naturalness. The results indicate that the new shoulder actuation is slightly better than a ball-and-socket-type actuation. However, the differences are small, and under the tested conditions, the comfort and the naturalness of the two tested shoulder actuations do not differ a lot.