BACKGROUND: Functional electrical stimulation (FES) cycling provides an exercise opportunity for people with multiple sclerosis (MS) who are nonambulatory. This study evaluated the efficacy of FES cycling for reducing fatigue and improving quality of life in people with MS who are nonambulatory and compared outcomes with those in a control group that did not take part in FES cycling. METHODS: Adults with MS with self-reported Expanded Disability Status Scale scores of 7.0 to 8.5 were randomized into a training group (n = 12) or a control group (n = 9). The training group performed FES cycling for 30 minutes, two to three times a week for 12 weeks. The primary outcome was safety, measured as the number and type of adverse events and any increase in symptoms. Other outcomes collected before and after the intervention were scores on the modified Ashworth Scale, manual muscle test, 5-item Modified Fatigue Impact Scale (MFIS-5), Fatigue Scale for Motor and Cognitive Functions (FSMC), Medical Outcomes Study Pain Effects Scale, Patient Health Questionnaire-9 (PHQ-9), Multiple Sclerosis Quality of Life-54 (MSQOL-54), and Exercise Self-Efficacy Scale. RESULTS: Twelve participants completed the study and were analyzed. Six participants completed training with no adverse events. The MFIS-5 (Cohen's d = 0.60), FSMC (Cohen's d = 0.37), and PHQ-9 (Cohen's d = 0.67) scores and the physical health composite of the MSQOL-54 (Cohen's d = 1.48) improved for the training group compared with the control group (n = 6). CONCLUSIONS: Functional electrical stimulation cycling is safe for people with MS who are nonambulatory and may reduce fatigue and improve measurements of quality of life.