In the critical care setting, the focus of care during the first few weeks following acute brain injury is prevention of secondary brain injury by optimizing cerebral perfusion. Ensuring adequate oxygenation and perfusion of cerebral tissues requires attention to all of the body systems. Chest percussion therapy (CPT) promotes pulmonary hygiene and optimizes gas exchange by opening the alveoli. However, many patients with brain injury have intracranial pressure (ICP) monitoring, and conventional wisdom supports limiting activities such as CPT that may stimulate the patient and increase ICP. The purpose of this study was to explore the effects of CPT on ICP. Thirty participants were enrolled over a 6-month period. Data were collected at 1-minute intervals for 1 hour. Each patient was randomized to receive automated CPT (using specialty beds) for 10 minutes, starting at 10, 20, 30, or 40 minutes into the hour. There were no differences in mean ICP values before, during, or after CPT. This study provides evidence that it is safe to perform CPT in patients with ICP monitoring in situ.