Introduction <p>The intracranial pressure (ICP) waveform conveys important information regarding the state of intracranial physiology, but in clinical practice it is typically analyzed in a qualitative fashion. We sought to develop a minimized model of intracranial physiology that describes intracranial dynamics occurring in a single cardiac cycle. By using an abridged model to which inputs of measured arterial and ICP waveforms from patients with brain injury can be applied, we aimed to derive estimates of intracranial elastance and venous outflow resistance.</p> Methods <p>The minimized model has two capacitor elements, representing arterial wall and intracranial compliance, and two resistance elements, representing intracranial viscoelasticity and venous outflow resistance. We use a parameter optimization method to achieve estimates of intracranial elastance and venous outflow resistance. We studied patients with brain injury in the neurointensive care unit who underwent ICP monitoring and analyzed data from periods of normal and elevated ICP.</p> Results <p>We studied 375 ICP waveforms in 15 patients. Model-derived waveforms corresponded closely to measured ICP waveforms at both normal and elevated ICP. Model-derived estimates of intracranial elastance and venous outflow resistance both increased significantly when ICP was elevated (mean increase of 1.0&#xa0;mm Hg/mL and 0.9&#xa0;mm Hg × s/mL, respectively).</p> Conclusions <p>The minimized model closely replicates measured ICP waveforms and allows for estimation of intracranial elastance and venous outflow resistance in patients with brain injury from readily available clinical parameters.</p>