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Background and Purpose: Patients with prolonged disorders of consciousness (pDoC) have a high mortality rate due to medical complications. Because an accurate prognosis is essential for decision-making on patients' management, we analysed data from an international multicentre prospective cohort study to evaluate 2-year mortality rate and bedside predictors of mortality., Methods: We enrolled adult patients in prolonged vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS) after traumatic and nontraumatic brain injury within 3 months postinjury. At enrolment, we collected demographic (age, sex), anamnestic (aetiology, time postinjury), clinical (Coma Recovery Scale-Revised [CRS-R], Disability Rating Scale, Nociception Coma Scale-Revised), and neurophysiologic (electroencephalogram [EEG], somatosensory evoked and event-related potentials) data. Patients were followed up to gather data on mortality up to 24 months postinjury., Results: Among 143 traumatic (n = 55) and nontraumatic (n = 88) patients (VS/UWS, n = 68, 19 females; MCS, n = 75, 22 females), 41 (28.7%) died within 24 months postinjury. Mortality rate was higher in VS/UWS (42.6%) than in MCS (16%; p < 0.001). Multivariate regression in VS/UWS showed that significant predictors of mortality were older age and lower CRS-R total score, whereas in MCS female sex and absence of alpha rhythm on EEG at study entry were significant predictors., Conclusions: This study demonstrated that a feasible multimodal assessment in the postacute phase can help clinicians to identify patients with pDoC at higher risk of mortality within 24 months after brain injury. This evidence can help clinicians and patients' families to navigate the complex clinical decision-making process and promote an international standardization of prognostic procedures for patients with pDoC., (© 2021 European Academy of Neurology.)