Project summary Stroke is a leading cause of death and permanent disability. Cardiovascular diseases are commonly presented and are primary causes of death in stroke survivors. Numerous studies have proven the benefits of walking or other forms of aerobic exercise for cardiovascular and pulmonary function in people after stroke. Most of the past studies targeted stroke survivors with mild or moderate sensorimotor impairment who can walk independently but did not include 22% or more of stroke survivors who remain non- ambulatory despite intensive rehabilitation. Upright walking may be a superior intervention to improve cardiovascular and pulmonary health in non-ambulatory chronic stroke survivors compared to sitting exercises that are commonly used. Current clinical guidelines could not make a clear recommendation as regarding to gait training for non-ambulatory chronic stroke survivors because they have been rarely enrolled in trials of gait training. Consequently, gait training is often not included in their rehabilitation plans despite its tremendous potential. The American Heart Association/American Stroke Association guidelines recognize this gap in our knowledge and strongly encourage research to explore broader application and effectiveness of assisted gait training in managing risk factors of cardiovascular and pulmonary diseases in non-ambulatory stroke survivors. To address this gap, the proposed randomized controlled efficacy trial will primarily examine whether our gait training can improve cardiovascular system in non-ambulatory chronic stroke survivors better than a sitting leg cycling exercise. We have recently developed a novel gait training device and a training program. A detailed description of the technical advantages of our device and promising pilot results of our gait training program are presented in the text of this application to support our scientific rationale. Our primary aim is to investigate the efficacy of an 8-week gait training program in comparison to an 8-week sitting leg cycling exercise program of a control group. Our primary hypothesis is that the gait training will result in significantly different changes in a positive direction in resting heart rate (rHR), systolic blood pressure (SBP), and glycated hemoglobin (HbA1c) than the sitting leg cycling exercise in non-ambulatory chronic stroke survivors, as demonstrated through a comparison between the experimental and control groups. To accomplish this goal, 90 non-ambulatory chronic stroke survivors will be recruited into the study. Individuals will be randomly allocated to an intervention (n = 45) or control (n = 45) group. The intervention group will receive three sessions of walking exercise each week for eight weeks along with usual care. The subjects in the control group will receive a sitting leg cycling exercise program. The proposed project will examine differences between the two groups in a set of comprehensive outcome assessments of cardiovascular, ...