Objective: To evaluate whether inspiratory muscle training (IMT) improves inspiratory muscle strength, respiratory capacity, fatigue, and subjective perception of physical endurance in patients with advanced multiple sclerosis (MS). Design: Randomized controlled trial. Setting: Outpatient clinic in Sweden. Participants: Fifteen severely disabled patients with MS, randomized to a training or control group. Intervention: Seven patients trained with a Threshold inspiratory muscle trainer, twice every other day, with 3 sets of 10 loaded inspirations (40%-60% of patients' maximal inspiratory pressure [PImax]) over a 10-week period. Main Outcome Measures: Spirometry, PImax, maximal expiratory pressure (PEmax), clinical assessments, and questionnaires on the patients' fatigue severity and physical endurance were evaluated. Results: After training, the PImax (P<.008) and PEmax (P<.02) increased in the training group. The improvement in PImax after 10 weeks of training was higher than the improvement in the control group (P<.01) and was maintained 1 month after the training period ended. The training affected neither respiratory function nor the patients' symptoms. Conclusions: IMT had a beneficial effect on inspiratory muscle strength in patients with MS and is recommended as a complement to ordinary physical training.