Raised intracranial pressure (ICP) is a key concern following acute brain injury as it may be associated with cerebral hypoperfusion and poor outcome. In this research we describe a mathematical physiological model designed to interpret cerebral physiology from neuromonitoring: ICP, near-infrared spectroscopy and transcranial Doppler flow velocity. This aims to characterise the complex dynamics of cerebral compliance, cerebral blood volume, cerebral blood flow and their regulation in individual patients. Analysis of data from six brain-injured patients produces cohesive predictions of cerebral biomechanics suggesting reduced cerebral compliance, reduced volume compensation and impaired blood flow autoregulation. Patient-specific physiological modelling has the potential to predict the key biomechanical and haemodynamic changes following brain injury in individual patients, and might be used to inform individualised treatment strategies.