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Introduction: Several studies have demonstrated the feasibility of individualizing optimal mean arterial blood pressure (MAP) with cerebral autoregulation (CA). However, it is still unclear whether cerebral autoregulation-oriented therapy has the potential to improve outcomes in critically ill patients. This study aimed to determine whether comatose patients with greater duration and magnitude of MAP outside the optimal arterial blood pressure (MAPOPT) have worse neurologic outcome than those with MAP closer to their MAPOPTcalculated bedside by CA monitoring.Methods: Cerebral oximetry index (COx) was continuously monitored with near-infrared spectroscopy (NIRS) for up to three days in acutely comatose patients admitted to a neurocritical care unit. MAPOPTwas calculated using the lowest COx (nadir index) every day of monitoring. Multivariate logistic regression was used to determine if survival at discharge was associated with lesser duration and magnitude of MAP outside the calculated MAPOPT.Results: A total of 74 patients were prospectively enrolled in the study. The median MAPOPT was 90 mmHg (IQR: 82.8-102.5 mmHg). The absolute difference between MAP and MAPOPTwas significantly associated with in-hospital mortality (OR=1.24, 95%CI=1.00-1.52, P=0.046) after adjusting for mRS on admission, brain herniation, midline shift at septum, Glasgow coma scale (GCS) score at the time of monitoring and duration of time under and above the MAPOPT. Other variables that reached statistical significance for mortality in the multivariate model were the duration of time under or above the MAPOPT (OR=1.11, 95%CI=1.02-1.21, P=0.016), midline shift at septum (OR=1.30, 95%CI=1.03-1.63, P=0.025) and GCS at the time of monitoring (OR=0.44, 95%CI=0.24-0.82, P=0.01).Conclusions: We found that mortality at hospital discharge in comatose adults with acute neurological illness was independently associated with greater magnitude and duration of MAP outside the MAPOPT. Non-invasive individualized bedside calculation of MAPOPT seems to be feasible and might be a promising tool for CA oriented-therapy in comatose patients.