Patient position change and tracheal suctioning are routine interventions in mechanically ventilated traumatic brain injury (TBI) patients. We sought to better understand the impact of these interventions on intracranial pressure (ICP) and cerebral hemodynamics. We conducted a prospective study in TBI patients requiring ICP monitoring. The timing of position changes and suctioning episodes were recorded with concurrent blood pressure and ICP measurements. We collected data on 460 patient position changes and 204 suctioning episodes over 2404 h in 18 ventilated patients (mean age 34  years, median Glasgow Coma Score 4 [3-7]). We recorded 24 (20-31) positioning and 11 (6-18) suctioning episodes per patient, with 54% and 39% of position changes associated with ICP ≥22 mm Hg and cerebral perfusion pressure (CPP) <60 mm Hg, respectively, and 22% and 27% of suctioning episodes associated with an ICP ≥22 mm Hg and CPP <60 mm Hg. The median change in ICP was 11 (6-16) mm Hg after position changes and 3 (1-9) mm Hg after suctioning. Reduction in CPP to <60 mm Hg lasted ≥10 min in 17% of positioning and 11% of suctioning episodes. The baseline ICP and its amplitude were both predictive of a rise in ICP ≥22 mm Hg after positioning and suctioning episodes, whereas cerebral autoregulation was not. Baseline CPP was predictive of a decrease in CPP <60 mm Hg after both interventions. Increases in ICP and reductions in CPP are common following patient positioning and tracheal suctioning episodes. Frequently, these changes are substantial and sustained.