The objective of the present study was to analyze the effect of different load directions and durations following impact using a finite element (FE) model of the human head. A detailed FE model of the human head was developed and validated against available cadaver experiment data for three impact directions (frontal, occipital, and lateral). Loads corresponding to the same impact power were imposed in different directions. Furthermore, the head injury criterion (HIC), the recently proposed head impact power (HIP) criterion, as well as peak angular acceleration, and change in angular and translational velocity were evaluated with respect to the strain in the central nervous system (CNS) tissue. A significant correlation was found between experiments and simulations with regard to intracranial pressure data for a short-duration impulse and intracerebral acceleration characteristics for a long-duration impulse with a high-angular component. However, a poor correlation with the simulations was found for the intracranial pressures for the long-duration impulse. This is thought to be a result of air introduced to the intracranial cavity during experimental testing. Smaller relative motion between the brain and skull results from lateral impact than from a frontal or occipital blow for both the experiments and FE simulations. It was found that the influence of impact direction had a substantial effect on the intracranial response. When evaluating the global kinematic injury measures for the rotational pulses, the change in angular velocity corresponded best with the intracranial strains found in the FE model. For the translational impulse, on the other hand, the HIC and the HIP showed the best correlation with the strain levels found in the model.