BackgroundMultiple sclerosis (MS)-related fatigue limits participation in everyday activities and has a considerable impact on quality of life (QoL), thereby affecting productivity and employment. Outpatient education interventions involving energy conservation strategies and cognitive behavioral therapy techniques are helpful. However, no inpatient program is currently available. The inpatient energy management education (IEME) program is a novel group-based intervention that lasts for 6.5 h and is conducted by a trained occupational therapist (OT) during a 3-week period of inpatient rehabilitation. Persons with MS (pwMS) and OTs previously evaluated the IEME positively in a pilot study test run. The aim of this study was to evaluate the feasibility of a research protocol and collect preliminary data on the IEME effect size. MethodsTo assess the feasibility of conducting a randomized clinical trial, pwMS-related fatigue were recruited during a 3-week inpatient rehabilitation. Six IEME (experimental) group sessions or progressive muscle relaxation (PMR, control) group sessions comprised part of a personalized rehabilitation program. The recruitment and assessment procedures, dropout and follow-up assessment rates and the treatment fidelity were evaluated, and six telephone interviews were conducted with IEME participants after they returned home. Outcomes were fatigue impact, occupational performance, self-efficacy regarding energy conservation strategies, and QoL at baseline, discharge, and 4 months. Paired-sample and independent-samples t-tests were used to assess within- and between-group effects. Effect sizes were estimated using Cohen's d. ResultsBetween August and November 2017, 47 pwMS were included and randomized. The dropout rate (4.2%) was low and the sample was balanced. The PMR was a well-accepted control intervention. The OTs reported no problems in conducting the IEME, and treatment fidelity was high. IEME participants confirmed the adequacy of the IEME. Within-group differences in fatigue impact and some QoL dimensions at discharge were significant (p < 0.05) in both groups. The IEME alone resulted in significant improvements in self-efficacy regarding energy conservation strategies, with a large effect size (Cohen's d: 1.32; 95% CI: 0.54–2.1), and in the QoL physical functioning dimension at T2 (Cohen's d: 1.32; 95% CI: 2.11–0.53). IEME participants spent significantly less time in individual OT sessions. A sample size of 192 participants in a randomized controlled trial would be sufficient to detect clinically relevant between-group differences. ConclusionThis feasibility study has provided promising preliminary data about the effect of the IEME. The research protocol was confirmed to be feasible and a future study is justified. This study was registered in the German Clinical Trials Register (no. DRKS00011634).