Long weekly hours of keyboard use may lead to or aggravate carpal tunnel syndrome. The effects of typing on fluid pressure in the carpal tunnel, a possible mediator of carpal tunnel syndrome, are unknown. Twenty healthy subjects participated in a laboratory study to investigate the effects of typing at different wrist postures on carpal tunnel pressure of the right hand. Changes in wrist flexion/extension angle (p = 0.01) and radial/ulnar deviation angle (p = 0.03) independently altered carpal tunnel pressure; wrist deviations in extension or radial deviation were associated with an increase in pressure. The activity of typing independently elevated carpal tunnel pressure (p = 0.001) relative to the static hand held in the same posture. This information can guide the design and use of keyboards and workstations in order to minimize carpal tunnel pressure while typing. The findings may also be useful to clinicians and ergonomists in the management of patients with carpal tunnel syndrome who use a keyboard.