Background: Increased cerebral perfusion pressure (CPP)>70 mmHg has been associated with acute respiratory distress syndrome (ARDS) after traumatic brain injury (TBI). Since this reported association, significant changes in ventilation strategies and fluid management have been accepted as routine critical care. Recently, individualized perfusion targets using autoregulation monitoring suggest CPP titration>70 mmHg. Given these clinical advances, the association between ARDS and increased CPP requires further delineation. Objective: To determine the association between ARDS and increased CPP after TBI. Methods: We conducted a single-center historical cohort study investigating the association of increased CPP and ARDS after TBI. We collected demographic data and physiologic data for CPP, intracranial pressure, mechanical ventilation, cumulative fluid balance and delta/driving pressure (ΔP). We collected outcomes measures pertaining to duration of ventilation, intensive care unit admission length, hospitalization length and 6-month neurological outcome. Results: In total, 113 patients with severe TBI and multimodal neuromonitoring were included. In total, 16 patients (14%) developed ARDS according to the Berlin definition. There was no difference in the mean CPP during the first 7 days of admission between patients who developed ARDS (74 mmHg SD 18 vs. 73 mmHg SD 18, p=0.86) versus those who did not. Patients who developed ARDS had a higher ΔP (15 mmHg  vs. 12 mmHg , p=0.016) and lower lung compliance (35 ml/cmH2O  vs. 49 ml/cmH2O , p=0.024) versus those who did not. Conclusion: We did not observe an association between increased CPP and ARDS. Patients with ARDS had higher ΔP and lower lung compliance.