Objective: To develop work guidelines for wrist posture based on carpal tunnel pressure. Background: Wrist posture is considered a risk factor for distal upper extremity musculoskeletal disorders, and sustained wrist deviation from neutral at work may be associated with carpal tunnel syndrome. However, the physiologic basis for wrist posture guidelines at work is limited. Methods: The relationship of wrist posture to carpal tunnel pressure was examined in 37 healthy participants. The participants slowly moved their wrists in extension-flexion and radioulnar deviation while wrist posture and carpal tunnel pressure were recorded. The wrist postures associated with pressures of 25 and 30 mmHg were identified for each motion and used to determine the 25th percentile wrist angles (the angles that protect 75% of the study population from reaching a pressure of 25 or 30 mmHg). Results: Using 30 mmHg, the 25th percentile angles were 32.7° (95% confidence interval [CI] = 27.2°—38.1°) for wrist extension, 48.6° (37.7°—59.4°) for flexion, 21.8° (14.7°—29.0°) for radial deviation, and 14.5° (9.6°—19.4°) for ulnar deviation. For 25 mmHg, the 25th percentile angles were 26.6° and 37.7° for extension and flexion, with radial and ulnar deviation being 17.8° and 12.1°, respectively. Conclusion: Further research can incorporate the independent contributions of pinch force and finger posture into this model. Application: The method presented can provide wrist posture guidelines for the design of tools and hand-intensive tasks.