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Severe acquired brain injuries (sABI) represent one of the main causes of disability and limitation in social life participation that need an intensive rehabilitation approach. The purpose of this study was to identify a possible correlation between different supposed conditioning factors and the efficiency of rehabilitation interventions. In this retrospective study, data were processed regarding 44 patients admitted to a neurorehabilitation department after sABI. A significant correlation with the efficiency of the rehabilitation intervention (expressed as the variation of the Barthel score between discharge and admittance in relation to the duration of the rehabilitative hospitalization) was found for both the etiology of the brain injury (p = 0.023), the precocity of the rehabilitation treatment (p = 0.0475), the presence of a tracheal cannula (p = 0.0084) and forms of nutrition other than oral (p < 0.0001). The results of this study suggest that improving the management of the respiratory system, swallowing and nutritional aspects, and favoring an early and personalized rehabilitation treatment, can help to optimize the overall care of patients suffering from sABI, thus allowing a reduction in complications, improvement in functional recovery and ensuring a better management of economic, social and health resources.