BACKGROUND: Using both hands is regularly needed for force/torque exertions in many activities, especially when using hand tools. OBJECTIVE: To investigate the effects of tool grip span, workpiece orientation, moving direction, and working height on two-handed wrist U/R deviation torque strength, usability, comfort, and discomfort while using locking pliers. METHODS: Participants (n = 22) took part in an experimental study which evaluated the effects of tool grip span (4.5–6.5 cm), workpiece orientation (transverse/sagittal), moving direction (clockwise (CW)/counterclockwise (CCW)), and working height (shoulder/elbow/knuckle) on two-handed wrist U/R deviation torque, (dis)comfort, and usability while using locking pliers. RESULTS: The results showed no significant effect of tool grip span on wrist U/R deviation torque strength, but the locking pliers with 4.5 cm handle grip span led to more comfort and better usability. The two-handed wrist U/R deviation torque strengths were significantly higher in sagittal plane than in transverse plane, and in CW direction than in CCW direction. The highest values of two-handed wrist U/R deviation torque strength in sagittal and transverse planes were exerted in knuckle and elbow heights, respectively. CONCLUSION: The findings can be used to develop guidelines and recommendations with regard to daily and occupational activities which require the use of both hands for force exertion with manual hand tools.