Developing new manual computer pointing devices abiding to the requirements set out in ergonomic product design literature necessitates joining contributions from several areas, including the ergonomic guidelines applicable to hand tool design, human–system interaction, and certain user characteristics such as anthropometric data. Computer mice are hand tools enabling the interaction with the computer, for use by people from both sexes and practically all ages. Moreover, the PC mouse’s intensive usage is able to cause musculoskeletal disorders. This paper reports on a study aimed at developing new computer mouse shapes, reducing forearm pronation, and providing hand–palm holding, supported by a literature review and an adequate design methodology, starting from known shapes of commercial products, the traditional (horizontal) computer mouse, and the vertical computer mouse. In this regard, potential concepts were generated as solutions to the previously specified problem through a set of creative tasks based on the specifications. Four new shapes were proposed to be evaluated through an assessment matrix; as a result, two new PC mice geometries were designed and fully prototyped. This study also reports on selected results of usability and an electromyographic evaluation of the prototypes against three commercial PC mice (horizontal, slanted, and vertical) by a sample of 20 participants, supporting validation of the development process and the newly developed geometries, with emphasis on the slanted conical innovative shape.