OBJECTIVE: Normal pressure hydrocephalus is not simply the result of a disturbance in CSF circulation, but often includes cardiovascular comorbidity and abnormalities within the cerebral mantle. In this study, the authors have examined the relationship between the global autoregulation pressure reactivity index (PRx), the profile of disturbed CSF circulation and pressure-volume compensation, and their possible effects on outcome after surgery. METHODS: The authors studied a cohort of 131 patients in whom a clinical suspicion of normal pressure hydrocephalus was investigated. Parameters describing CSF compensation and circulation were calculated during the CSF infusion test, and PRx was calculated from CSF pressure and mean arterial blood pressure (MAP) recordings. A simple scale was used to mark the patients’ outcome 6 months after surgery (improvement, temporary improvement, and no improvement). RESULTS: The PRx was negatively correlated with resistance to CSF outflow (R = -0.18; p = 0.044); patients with normal CSF circulation tended to have worse autoregulation. The correlation for patients who were surgically treated (n = 83) was R = -0.28; p = 0.01, and it was stronger in patients who experienced sustained improvement after surgery (n = 48, R = -0.43; p = 0.002). In patients who did not improve, the correlation was not significantly different from zero (n = 19, R = -0.07; p = 0.97). There was a trend toward higher values for PRx in nonresponders than in responders (0.16 ± 0.04 vs 0.09 ± 0.02, respectively; p = 0.061), associated with higher MAP values (107.2 ± 8.2 in nonresponders vs 89.5 ± 3.5 in responders; p = 0.195). The product of MAP × (1 + PRx), which was proposed as a measure of combined arterial hypertension and deranged autoregulation, showed a significant association with outcome (greater value in nonresponders; p = 0.013). CONCLUSION: Autoregulation proves to associate with CSF circulation and appears strongest in shunt responders. Outcome following CSF diversion is possibly most favorable when CSF outflow resistance is increased and global cerebral autoregulation is intact, in combination with arterial normotension.