In patients with severe traumatic brain injury, there is limited evidence of the clinical effect of early orthostatic exercise, although such exercise may strengthen systemic or cerebral hemodynamic responses to head-up tilt, thereby minimizing orthostatic intolerance. We measured dynamic cerebral autoregulation (dCA) and the occurrence of orthostatic intolerance after four weeks of regular orthostatic exercise by head-up tilt using a tilt table with integrated stepping using the ERIGO® tilt-table and comparing it to standard care. Thirty-four patients with severe traumatic brain injury admitted to a neurocritical care unit were included in this randomized clinical trial. Middle cerebral artery blood flow velocity (MCAv), non-invasive mean arterial pressure, heart rate and PaCO₂ were recorded; dCA was measured by the non-invasive mean flow index (nMxa). Transition from the supine position to head-up tilt triggered a 10–16% decrease in MCAv and increased nMxa in both groups at all time points (P < 0.05), with no differences between groups. There was no difference in the number of episodes with orthostatic intolerance (5 vs 3; 1 vs 2; 1 vs 0) at baseline, two weeks and four weeks, respectively, and no association between changes in PaCO₂-adjusted nMxa and the occurrence of orthostatic reactions (P = 0.35). Early orthostatic exercise does not affect dynamic cerebral autoregulation and does not protect against orthostatic intolerance in patients with severe traumatic brain injury. Trial registration: ClinicalTrials.gov identifier: NCT02924649. Registered on 3rd October 2016.