Recent single center retrospective analysis displayed the association between admission computed tomography (CT) markers of diffuse intra-cranial (IC) injury and worse cerebrovascular reactivity. The goal of this study is to further explore these associations using the prospective multi-center Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high resolution data set (HR ICU). Using the CENTER-TBI HR ICU sub-study cohort, we evaluated those patients with both archived high-frequency digital physiology (100 Hz or higher), and the presence of a digital admission CT scan. Physiologic signals were processed for pressure reactivity index (PRx) and both the % time above defined PRx thresholds and mean hourly dose above threshold. Admission CT injury scores were obtained from the database. Quantitative contusion, edema, intraventricular hemorrhage (IVH) and extra-axial lesion volumes were obtained via semi-automated segmentation. Comparison between admission CT characteristics and PRx metrics was conducted using Mann-U, Jonckheere Terpstra testing, with a combination of univariate linear and logistic regression techniques. A total of 165 patients were included. Cisternal compression and high admission Rotterdam and Helsinki CT scores, and Marshall CT diffuse injury sub-scores were associated with increased % time and hourly dose above PRx threshold of 0, +0.25 and +0.35 (p<0.02 for all).Logistic regression analysis displayed an association between deep peri-contusional edema and mean PRx above threshold of +0.25. These results suggest that diffuse injury patterns, consistent with acceleration/deceleration forces, are associated with impaired cerebrovascular reactivity. Diffuse admission IC injury patterns appear to be consistently associated with impaired cerebrovascular reactivity, as measured through PRx. This is in keeping with the previous single center retrospective literature on the topic. This study provides multicenter validation for those results, and provide preliminary data to support potential risk stratification for impaired cerebrovascular reactivity based on injury pattern.