Hand tools such a computer mice are designed by an iterative process of matching needs and characteristics of people to mechanical (hardware) and system (software) requirements. Comfort is one such human need. The location and amount of hand support or contact between users' hands and computer mice, in addition to other factors, may influence users' perceived comfort. Real-time infrared thermography was used to qualify and quantify heat signatures after brief periods of contact. Three uniquely different Microsoft computer mice were investigated. Participants were instructed to hold mice as they expected during use or as they remembered using during a target acquisition task. An infrared image was recorded of the palmar surface of the participant's hand and the top of computer mouse. Subjective perceptions of comfort were collected using Likert scales related to comfort, fit, control, maneuverability, and performance. Participants' preference rankings were also collected. The technique was sensitive enough to measure unique differences in contact area between participants' hands and the different computer mice. The amount of contact under the metacarpophalangeal ridge (i.e., pads of palm under knuckles) was related to the level of perceived comfort and preferences. This study demonstrated the utility of infrared thermography with subjective comfort impressions for qualitatively and quantitatively evaluating computer mouse designs.