Decompressive Craniectomy (DC) is a neurosurgical procedure which is often applied to decrease the intracranial pressure (ICP), even if its optimal execution in terms of the size and location of the skull opening is not known. The current research focuses on DC from a biomechanical perspective. A finite element (FE) modelling strategy is applied where patient-specific head models are developed. These numerical models are used to perform virtual experiments where DC is simulated several times with skull openings having different size and location. During the simulations ICP, stress and strain distributions in the brain tissue are monitored in the function of the skull opening details. In the knowledge of these objective functions suggestions could be made regarding the applied optimization procedure which can lead to the identification of optimal DC scenarios in the future.