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Background: There is a pressing need for scalable healthcare solutions and a shift in the rehabilitation paradigm from hospitals to homes to tackle the increase in stroke incidence while reducing the practical and economic burden for patients, hospitals, and society. Digital health technologies can contribute to addressing this challenge; however, little is known about their effectiveness in at-home settings. In response, we have designed the RGS@home study to investigate the effectiveness, acceptance, and cost of a deep tech solution called the Rehabilitation Gaming System (RGS). RGS is a cloud-based system for delivering AI-enhanced rehabilitation using virtual reality, motion capture, and wearables that can be used in the hospital and at home. The core principles of the brain theory-based RGS intervention are to deliver rehabilitation exercises in the form of embodied, goal-oriented, and task-specific action., Methods: The RGS@home study is a randomized longitudinal clinical trial designed to assess whether the combination of the RGS intervention with standard care is superior to standard care alone for the functional recovery of stroke patients at the hospital and at home. The study is conducted in collaboration with hospitals in Spain, Sweden, and France and includes inpatients and outpatients at subacute and chronic stages post-stroke. The intervention duration is 3 months with assessment at baseline and after 3, 6, and 12 months. The impact of RGS is evaluated in terms of quality of life measurements, usability, and acceptance using standardized clinical scales, together with health economic analysis. So far, one-third of the patients expected to participate in the study have been recruited (N = 90, mean age 60, days after stroke ≥ 30 days). The trial will end in July 2023., Discussion: We predict an improvement in the patients' recovery, high acceptance, and reduced costs due to a soft landing from the clinic to home rehabilitation. In addition, the data provided will allow us to assess whether the prescription of therapy at home can counteract deterioration and improve quality of life while also identifying new standards for online and remote assessment, diagnostics, and intervention across European hospitals., Trial Registration: C linicalTrials.gov NCT04620707. Registered on November 3, 2020., (© 2022. The Author(s).)