Electromagnetic-field therapy has beneficial short-term effects in multiple sclerosis (MS) patients with major fatigue, but long-term data are lacking. PRIMARY STUDY OBJECTIVES: To evaluate the long-term effects of a specific electromagnetic therapy device (Bio-Electromagnetic- Energy-Regulation BEMER) on MS-related fatigue, we designed a crossover control of a previously performed randomized controlled trial and a long-term open-label follow-up trial.Crossover and open-label follow-up trials at a single neurological outpatient center.Patients with relapsing-remitting MS who had major fatigue (N = 37 patients).After a previous randomized controlled trial (exposure to low-frequency pulsed magnetic fields for 8 min twice daily or to placebo treatment for 12 wk), a crossover from control to treatment for another 12 weeks, followed by an open label follow-up trial to 3 years, were done.The outcome criteria were the Modified Fatigue Impact Scale (MFIS), Fatigue Severity Scale (FSS), German long version of the Center for Epidemiologic Studies Depression Scale (CES-D), Multiple Sclerosis Functional Scale (MSFC), and Expanded Disability Status Scale (EDSS).Patients previously on placebo during the randomized controlled trial experienced significant reductions in fatigue after crossing over to treatment. The MFIS and FSS scores were significantly lower in the open-label group than in the control subjects after follow-up. Participation in the open-label treatment was the strongest predictor of low fatigue outcome after followup. Electromagnetic-field therapy was well tolerated.In this long-term study, a beneficial effect of long-term BEMER therapy on MS fatigue was demonstrated. Electromagnetic-field therapy may be a useful therapeutic modality in MS patients with severe fatigue.