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Background: Many children with physical disabilities lack independent mobility. Powered wheelchair mobility can be a viable option, but users must be proficient drivers to ensure safety. To become a proficient driver, children need opportunities to practice. As is often the case, powered wheelchairs are scarce and direct therapy hours dedicated to powered mobility are often limited. Alternative options are needed to enable safe, unsupervised practice. Simulator-based learning has been shown to be an effective training method for powered mobility and other skill-based tasks for adults. The goal of this study was to compare two training methods of powered mobility, powered wheelchair practice (control group) versus simulator-based (experimental group) practice to determine whether simulation is a feasible and effective method for children and adolescents. The hypothesis was that children practicing on either modality at home supervised by a caregiver would similarly improve their powered mobility skills. Method: Participants included 36 children and adolescents (23 males, 13 females) with cerebral palsy and neuromuscular diseases, aged 6-18 years (mean age: 10 y, 7 mo, SD: 3y, 7 mo). Data were collected and compared at baseline and after 12 weeks of home based practice of powered mobility via a powered wheelchair or a simulator. Thirty participants completed the study and were included in the analysis Powered mobility ability was determined by the Powered Mobility Program (PMP), the Israeli Ministry of Health’s Powered Mobility Proficiency Test (PM-PT) and the Assessment of Learning Powered Mobility use (ALP). Participants (21/30) were interviewed after study completion by an independent researcher concerning the child’s and parent’s experiences regarding practice time and user experience (e.g., satisfaction with training program, views of its importance). Results: Both the powered wheelchair and simulator-based practice groups achieved significant improvement following the practice period as assessed by the PMP and PM-PT assessments, with no significant difference between them. A significant improvement was found in the ALP assessment outcomes for the powered wheelchair group only. All participants practiced for the required amount of time and both groups reported a similar user experience. Conclusions: The results demonstrate that simulator-based practice is an effective training option for powered mobility for children aged 6-18 years old with physical disabilities. Simulator-based practice can provide a safe environment to practice driving skills that could endanger the child (e.g., out of doors). This is the first study, to our knowledge, that compares two different wheelchair training methods. Trial Registration: The study protocol for this clinical trial was registered at ClinicalTrials.gov under the ID NCT04531488 and the title “ Simulator Based Powered Mobility Training of Children With Special Needs ”(Protocol ID: 004-17, URL: https://rb.gy/dfeslr).