Objective.This international multi-center, prospective, observational study aimed at identifying predictors of short-term clinical outcome in patients with prolonged Disorders of Consciousness (DoC) due to acquired severe brain injury.Methods.Patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS) or in minimally conscious state (MCS) were enrolled within 3 months from their brain injury in 12 specialized medical institutions. Demographic, anamnestic, clinical and neurophysiological data were collected at study entry. Patients were then followed-up for assessing the primary outcome, i.e. clinical diagnosis according to standardized criteria at 6 months post-injury.Results.We enrolled 147 patients (44 women; mean age: 49.4 [95% confidence intervals: 46.1-52.6] years; VS/UWS= 71, MCS= 76; traumatic= 55, vascular= 56, anoxic= 36; mean time post-injury= 59.6 [55.4-63.6] days). The 6-month follow-up was complete for 143 patients (VS/UWS= 70; MCS= 73). With respect to study entry, the clinical diagnosis improved in 72 patients (VS/UWS= 27; MCS= 45). Younger age, shorter time post-injury, higher Coma Recovery Scale-Revised total score and presence of EEG reactivity to eye opening at study entry predicted better outcome, whereas etiology, clinical diagnosis, Disability Rating Scale score, EEG background activity, acoustic reactivity and P300 on event related potentials were not associated with outcome.Conclusions.Multimodal assessment could identify patients with higher likelihood of clinical improvement in order to help clinicians, families and funding sources with various aspects of decision-making. This multi-center, international study aims to stimulate further research that drives international consensus regarding standardization of prognostic procedures for patients with DoC.