BACKGROUND: In traumatic brain injury (TBI), swelling may disturb the potentially uniform pressure distribution in the brain, producing sustained intercompartmental pressure gradients which may associate with midline shift. The presence of pressure gradients is often neglected since bilateral invasive intracranial pressure (ICP) monitoring is not usually considered because of risks and high costs. We evaluated the presence of interhemispheric pressure gradients using bilateral transcranial Doppler (TCD) as means for noninvasive ICP (nICP) monitoring in TBI patients presenting midline shift. METHODS: From a retrospective cohort of 97 TBI patients with arterial blood pressure (ABP), ICP and bilateral TCD monitoring, 24 presented unilateral lesion and midline shift confirmed by computer tomography. nICP and noninvasive cerebral perfusion pressure (nCPP) on the left and right brain hemispheres were retrospectively calculated using a mathematical model associating TCD-derived cerebral blood flow velocity and ABP. RESULTS: The nCPP difference was correlated with midline shift (R=-0.34, P<0.01) showing a tendency to record higher CPP at the side of expansion. Accordingly, nICP at the side of expansion was significantly lower in comparison to the compressed side (18.86 [±5.71] mmHg [mean±standard deviation] versus 20.30 [±6.78] mmHg for expansion and compressed sides, respectively). Subsequently, nCPP was greater on the side of brain expansion (79.48±7.84, 78.03±8.93 mmHg [P<0.01], for expansion and compressed sides, respectively). CONCLUSIONS: TCD-based interhemispheric nCPP difference showed significant correlation with midline shift. Cerebral perfusion pressure was greater on the side of brain expansion, acting as the driving force to shift brain structures.