The objective of the present study was to analyze the effect of different loading directions following impact, and to evaluate existing global head injury criteria. Detailed and parameterized models of the adult human head were created by using the Finite Element Method (FEM). Loads corresponding to the same impact power were imposed in different directions. Furthermore, the Head Injury Criterion (HIC) and the recently proposed Head Impact Power (HIP) criterion were evaluated with respect to the relative motion between the skull and the brain, as well as the strain in the bridging veins. It was found that the influence of impact direction had a substantial effect on the intracranial response. The largest relative skull-brain motion and strain in the bridging veins occurred with the anterior-posterior (AP) and posterior-anterior (PA) rotational impulses. HIC was unable to predict consequences of a pure rotational impulse while HIP needed individual scaling coefficients for the different terms to account for difference in load direction. When using the proposed scaling procedure, a better prediction of subdural hematoma (SDH) was obtained. It is thus suggested that an evaluation of the synergistic terms is necessary to further improve the injury prediction. These variations should be considered when developing new head injury criteria.