Health benefits of physical activity are well recognized in the general population for reducing the risk of chronic health conditions. Less is known about the effects of physical activity on people currently using or who may use wheeled mobility devices in the future, specifically individuals with multiple sclerosis, cerebral palsy, and spinal cord injury who are at increased likelihood for use of a wheeled mobility device. On December 1-3, 2020, the National Institutes of Health convened the Pathways to Prevention workshop: "Can Physical Activity Improve the Health of Wheelchair Users?" to consider the available scientific evidence on the clinical benefits and harms of physical activity for people currently using or who may use wheeled mobility devices in the future, with the aim of developing recommendations to fill gaps in the evidence base. A multidisciplinary team of content area experts developed the agenda and an evidence-based practice center prepared the evidence report. An independent panel, selected by the National Institutes of Health, attended the workshop; convened to develop recommendations on the basis of the systematic review, presentations, and public comments received during the workshop; and revised recommendations based on public comments received. This final report summarizes the panel's findings and identifies current gaps in knowledge. The panel made recommendations for new research efforts, including novel methods and new research infrastructure to improve the evidence base about the effects of physical activity on people currently using or who may use wheeled mobility devices in the future.