Background:Severe acquired brain injury (SABI) rehabilitation should be as intensive and long as to allow the patients get the best independence and quality of life (QoL), but facing with the rehabilitation socioeconomic burden. Telerehabilitation (TR) could supply frail subjects requiring long-term rehabilitation.Methods:A multicenter, prospective, parallel design, single-blind trial will be conducted at the IRCCS Neurolesi Bonino Pulejo (Messina, Italy) and IRCCS Hospital San Camillo (Venice, Italy) involving patients suffering from SABI and requiring home motor and cognitive rehabilitation. We will investigate the use of TR, based on advanced Information and Communication Technology (ICT) solutions, taking into account that the supervision of rehabilitation at home will be enriched with the counseling and vital parameters monitoring. The enrolled patients will be balanced for pathology, and randomized in 2 groups, performing TR (G1) or standard rehabilitation training (G2), respectively, according to a pc-generated random assignment. TR will be delivered by means of an advanced video-conferencing system, whereas the patient will be provided with low-cost monitoring devices, able to collect data about his/her health status and QoL. In both the groups each treatment (either cognitive or motor, or both as per patient functional status) will last about 1 hour a day, 5 days/week, for 12 weeks. Two structured telephone interviews will be administered to the patients (when possible) and/or their caregivers, and to all the healthcare professionals involved in the patient management, 1 week after the beginning and at the end of the TR. All the patients will undergo a complete neurological and cognitive examination performed by skilled physicians and psychologists, blindly. Clinical evaluations will be administered blindly, before and after the treatments.Results:the data of this study should demonstrate that TR is at least non-inferior in comparison with the same amount of usual territorial rehabilitative physical treatments, taking into account patients’ functional recovery, psychological well-being, caregiver burden, and healthcare costs.Conclusion:data coming from this study could demonstrate the usefulness of TR in facing the rehabilitation socioeconomic burden of managing patients with SABI, so to allow the patients get the best independence and quality of life (QoL).