An estimated 1.7 million people in the United States sustain a traumatic brain injury (TBI) annually. To investigate the effects of rotational motions on TBI risk and location, this study modeled rotational velocities of five magnitudes and 26 directions of rotation using the Simulated Injury Monitor finite element brain model. The volume fraction of the total brain exceeding a predetermined strain threshold, the Cumulative Strain Damage Measure (CSDM), was investigated to evaluate global model response. To evaluate regional response, this metric was computed relative to individual brain structures and termed the Structure Cumulative Strain Damage Measure (SCSDM). CSDM increased as input magnitude increased and varied with the direction of rotation. CSDM was 0.55-1.7 times larger in simulations with transverse plane rotation compared to those without transverse plane rotation. The largest SCSDM in the cerebrum and brainstem occurred with rotations in the transverse and sagittal planes, respectively. Velocities causing medial rotation of the cerebellum resulted in the largest SCSDM in this structure. For velocities of the same magnitude, injury risk calculated from CSDM varied from 0 to 97% with variations in the direction of rotation. These findings demonstrate injury risk, as estimated by CSDM and SCSDM, is affected by the direction of rotation and input magnitude, and these may be important considerations for injury prediction.