Reliable and noninvasive assessment of cerebral blood flow regulation is a major challenge in acute care monitoring. This study assessed dynamics of flow regulation and its relationship to asymmetry of initial computed tomography (CT) scan using multimodal pressure flow (MMPF) analysis. Data of 27 patients (38 ± 15 years old) with traumatic brain injury (TBI) were analyzed. Patients were selected from bigger cohort according to criteria of having midline shift on initial CT scan and intact skull (no craniotomy or bone flap). The MMPF analysis was used to extract the oscillations in cerebral perfusion pressure (CPP) and blood flow velocity (BFV) signals at frequency of artificial ventilation, and to calculate the instantaneous phase difference between CPP and BFV oscillations. Mean CPP-BFV phase difference was used to quantify pressure and flow relationship. The TBI subjects had smaller mean BP-BFV phase shifts (left, 8.7 ± 9.6; right 10.2 ± 8.3 MCAs, mean ± SD) than values previously obtained in healthy subjects (left, 37.3 ± 7.6 degrees; right, 38.0 ± 8.9 degrees; p < 0.0001), suggesting impaired blood flow regulation after TBI. The difference in phase shift between CPP and BFV in the left and right side was strongly correlated to the midline shift (R = 0.78; p < 0.0001). These findings indicate that the MMPF method allows reliable assessment of alterations in pressure and flow relationship after TBI. Moreover, mean pressure-flow phase shift is sensitive to the displacement of midline of the brain, and may potentially serve as a marker of asymmetry of cerebral autoregulation.