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Objective. The objective of this study was to determine the feasibility of low-load resistance training with blood flow restriction (BFR) for people with advanced disability due to multiple sclerosis (MS). Methods. In this prospective cohort study, 14 participants with MS (Expanded Disability Status Scale [EDSS] score = 6.0 to 7.0; mean age = 55.4 [SD = 6.2] years; 71% women) were asked to perform 3 lower extremity resistance exercises (leg press, calf press, and hip abduction) bilaterally twice weekly for 8 weeks using BFR. Feasibility criteria were as follows: enrollment of 20 participants, [greater than or equal to] 80% retention and adherence, [greater than or equal to] 90% satisfaction, and no serious adverse events related to the intervention. Other outcomes included knee extensor, ankle plantar flexor, and hip abductor muscle strength, 30-Second Sit-to-Stand Test, Berg Balance Scale, Timed 25-Foot Walk Test, 12-Item MS Walking Scale, Modified Fatigue Impact Scale, Patient-Specific Functional Scale, and daily step count. Results. Sixteen participants consented, and 14 completed the intervention, with 93% adherence overall. All participants were satisfied with the intervention. A minor hip muscle strain was the only intervention-related adverse event. There were muscle strength improvements on the more-involved (16%-28%) and less-involved (12%-19%) sides. There were also changes in the 30-Second Sit-to-Stand Test (1.9 repetitions; 95% CI = 1.0 to 2.8), Berg Balance Scale (5.3 points; 95% CI = 3.2 to 7.4), Timed 25-Foot Walk Test (-3.3 seconds; 95% CI = -7.9 to 1.3), Modified Fatigue Impact Scale (-8.8 points; 95% CI = -16.5 to -1.1), 12-Item MS Walking Scale (-3.6 points; 95% CI = -11.5 to 4.4), Patient-Specific Functional Scale (2.9 points; 95% CI = 1.9 to 3.8), and daily step count (333 steps; 95% CI = -191 to 857). Conclusion. Low-load resistance training using BFR in people with MS and EDSS scores of 6.0 to 7.0 appears feasible, and subsequent investigation into its efficacy is warranted. Impact. Although efficacy data are needed, combining BFR with low-load resistance training may be a viable alternative for people who have MS and who do not tolerate conventional moderate- to high-intensity training because of more severe symptoms, such as fatigue and weakness. Lay Summary. Low-load strength training with BFR was feasible in people who have advanced disability due to MS. Using BFR may provide an alternative for people with MS who do not tolerate higher intensity training due to more severe symptoms, such as fatigue and weakness. Keywords: Blood Flow Restriction, Feasibility, Low-Load Resistance Training, Multiple Sclerosis, Introduction Multiple sclerosis (MS) is an autoimmune condition that causes demyelination and axonal death in the central nervous system, and can result in a variety of symptoms depending on lesion [...]