© 2020 Elsevier GmbHIntroduction: Imbalance, mobility impairment, and fatigue are common in Multiple Sclerosis (MS) patients. Virtual reality (VR) promises to be an effective and enjoyable tool for the rehabilitation of these symptoms. Immersive virtual reality (IVR) with a head-mounted display (HMD) enhances the perception of reality. The purpose of this study was to investigate the efficacy of IVR training on balance, mobility, and fatigue in patients with MS. Methods: The patients were randomly divided into three groups; the immersive virtual reality group (IVRG, n:17), the balance training group (BTG, n:17) and the control group (CG, n:17). The IVRG and BTG received the training twice a week for 8 weeks. The CG performed only relaxation exercises at home. All patients were evaluated at baseline and after eight weeks by the Berg Balance Scale (BBS), posturography, Timed Up and Go (TUG), and Fatigue Severity Scale (FSS). Results: The balance assessed with BBS increased in only BTG (p < 0.05). The postural stability on eyes open-firm surface and eyes closed-foam surface improved in both training groups (p < 0.05) without any inter-group superiority (p > 0.05). However, the postural stability on eyes closed-firm surface in only IVRG and the single-leg stability on the right foot in only BTG improved (p < 0.05). In addition, overall limits of stability, fatigue, and mobility under both the single-task and cognitive dual-task conditions improved in both training groups (p < 0.05) without any inter-group superiority (p > 0.05). In the CG, the postural sways on both right and left single foot increased (p < 0.05) while overall limits of stability, mobility, and fatigue did not change significantly (p > 0.05). Conclusions: IVR training has beneficial effects similar to those of balance training on balance, mobility, and fatigue in patients with MS and could be used as an effective integrative method for balance training in patients with MS.