The goal of this study was to evaluate the effect of different types of computer pointing devices and placements on posture and muscle activity of the hand and arm. A repeated measures laboratory study with 12 adults (6 females, 6 males) was conducted. Participants completed two mouse-intensive tasks while using a conventional mouse, a trackball, a stand-alone touchpad, and a rollermouse. A motion analysis system and an electromyography system monitored right upper extremity postures and muscle activity, respectively. The rollermouse condition was associated with a more neutral hand posture (lower inter-fingertip spread and greater finger flexion) along with significantly lower forearm extensor muscle activity. The touchpad and rollermouse, which were centrally located, were associated with significantly more neutral shoulder postures, reduced ulnar deviation, and lower forearm extensor muscle activities than other types of pointing devices. Users reported the most difficulty using the trackball and touchpad. Rollermouse was not more difficult to use than any other devices. These results show that computer pointing device design and location elicit significantly different postures and forearm muscle activities during use, especially for the hand posture metrics.