Optical motion capture (OMC) systems are commonly used to capture in-vivo three-dimensional joint kinematics. However, the skin-based markers may not reflect the underlying bone movement, a source of error known as soft tissue artifact (STA). This study examined STA during wrist motion by evaluating the agreement between OMC and biplanar videoradiography (BVR). Nine subjects completed 7 different wrist motion tasks: doorknob rotation to capture supination and pronation, radial-ulnar deviation, flexion–extension, circumduction, hammering, and pitcher pouring. BVR and OMC captured the motion simultaneously. Wrist kinematics were quantified using helical motion parameters of rotation and translation, and Bland-Altman analysis quantified the mean difference (bias) and 95% limit of agreement (LOA). The rotational bias of doorknob pronation, a median bias of −4.9°, was significantly larger than the flexion–extension (0.7°, p < 0.05) and radial-ulnar deviation (1.8°, p < 0.01) tasks. The rotational LOA range was significantly smaller in the flexion–extension task (5.9°) compared to pitcher (11.6°, p < 0.05) and doorknob pronation (17.9°, p < 0.05) tasks. The translation bias did not differ between tasks. The translation LOA range was significantly larger in circumduction (9.8°) compared to the radial-ulnar deviation (6.3°, p < 0.05) and pitcher (3.4°, p < 0.05) tasks. While OMC technology has a wide-range of successful applications, we demonstrated it has relatively poor agreement with BVR in tracking wrist motion, and that the agreement depends on the nature and direction of wrist motion.