Background Research suggests that intracranial pressure (ICP) dynamics beyond just absolute ICP level provide information reflecting intracranial adaptive capacity. Specifically, evidence indicates that physiologic variability provides information about system functioning that may reflect dimensions of adaptive capacity. The purpose of this study was to examine the association between ICP variability in patients following moderate to severe traumatic brain injury (TBI) and outcome at hospital discharge and 6 months post-injury. Methods ICP was monitored continuously for 4 days in 147 patients (78% male; mean (SID) age=37 years (18 years)). ICP variability indices were calculated for four time scales (24 h, 60 min, 5 min and 5 s). Functional outcome was assessed using the Extended Glasgow Outcome Scale (GOSE). Logistic regression was used to estimate odds of survival or favorable outcome, and ordinal regression was used to estimate odds for outcome above versus below GOSE thresholds, predicted by ICP variability, controlling for age, gender, Glasgow Coma Scale motor score, craniectomy, and ICP level. Findings ICP variability indices were better predictors of 6-month outcome than mean ICP. Survival was significantly associated with greater 5-s ICP variability (p<0.001). Higher ICP variability on shorter time scales was associated with better functional outcome (5-s RMSSD, 5-min SD: p<0.002; 60-min SD: p<0.011). Conclusions ICP variability may reflect the degree of intactness of intracranial adaptive ability.