The University of Bologna and the INAIL Prosthesis Centre are collaborating to design new high-functionality prostheses for upper-limb amputees, with a high-level amputation, who are currently rehabilitated by inadequate commercial solutions. This study deals with the development of a new powered humeral rotator that should integrate the prosthesis previously developed by the research group, which is already provided with a terminal device, a wrist rotator, an elbow joint, and a prototype of shoulder articulation composed of two powered revolute joints. This paper focuses on the design methodology that was followed to retrieve the design input data necessary for the development of the humeral rotator. The methodology is mainly based on kinematic and kinetostatic analyses of multibody models of upper-limb prostheses. The kinematic simulations are used to define the ability of the arm models (that have less than the six degrees of freedom required for generically positioning and orienting the terminal device) satisfactorily to perform important activities of daily living, i.e. with an acceptable accuracy. Kinetostatic analyses are then performed to determine the loads acting on the humeral rotator when performing the mentioned activities, thus making it possible to define fundamental design guidelines and technical specifications.