The biomechanical stability of an internal fixation system that uses low-profile modular implants to stabilize individual fracture components was studied in a validated cadaver fracture model that incorporated physiologic muscle forces and wrist motion. Fragment-specific fixation with immediate range of motion was compared with static augmented external fixation in simulated, unstable 3- and 4-part intra-articular distal radius fractures (n = 20). Fixation was applied and specimens were loaded via their major wrist tendons. Because the wrist joint was not constrained in the internal fixation group, full wrist motion occurred during load application in these specimens. A 3-dimensional motion tracking system calculated individual fracture fragment motion in both groups. In the 3-part fracture pattern fragment-specific fixation showed comparable stability to static augmented external fixation despite the full wrist range of motion that occurred during application of load in these specimens. In the 4-part fracture pattern fragment-specific fixation was shown to be significantly more stable when compared with static augmented external fixation in 4 of 6 axes of motion. Our findings confirm the stability of this low-profile plating system and support the consideration of early wrist motion when treating complex, intra-articular distal radius fractures with fragment-specific fixation.