BACKGROUND: Muscle strength and dexterity impairments are common among patients with multiple sclerosis (MS) producing limitations in activities of daily living related to the upper limb (UL). This study aimed to evaluate the effectiveness of serious games specifically developed for the MYO Armband® capture sensor in improving forearm and wrist mobility, UL muscle strength, dexterity, fatigue, functionality, quality of life, satisfaction, adverse effects and compliance. METHODS: A double-blinded (allocation concealment was performed by a blinded investigator and by blinding for assessors) randomised controlled trial was conducted. The sample was randomised into two groups: an experimental group that received treatment based on UL serious games designed by the research team and controlled by the MYO Armband® gesture capture sensor, along with conventional rehabilitation and a control group that received the same conventional rehabilitation for the UL. Both groups received two 60-min sessions per week over an eight-week period. Wrist range of motion (goniometry), grip muscle strength (Jamar® dynamometer), coordination and gross UL dexterity (Box and Block Test), fatigue (Fatigue Severity Scale), functionality (ABILHAND), quality of life (Multiple Sclerosis Impact Scale-29), adverse effects (Simulator Sickness Questionnaire, SSQ), perceived workload (NASA-Task load index), satisfaction (Client Satisfaction Questionnaire-8 (CSQ-8), Satisfaction with Technology Scale, System Usability Scale (SUS) and QUEST 2.0) and compliance (attendance) were assessed in both groups pre-treatment, post-treatment and during a follow-up period of 2 weeks without receiving any treatment. RESULTS: Significant differences were observed in the experimental group compared to the control group in the assessment of forearm supination (p = .004) and grip strength (p = .004). Adverse effects were minimal (SSQ: 7/100 points) and perceived workload was low (NASA-Task Load Index: 25/100 points) in the experimental group. The MYO Armband® technology proved to be useful for the participants (SUS: 80.66/100) and the satisfaction scales received high scores (QUEST 2.0: 59.4/70 points; Satisfaction with Technology: 84.36/100 points). There were significant differences between the groups in terms of attendance percentage (p = .029). CONCLUSIONS: An experimental protocol using MYO Armband®-based serious games designed for UL rehabilitation showed improvements in active wrist range of motion and handgrip strength in patients with MS, with high satisfaction, minimal adverse effects and workload and excellent compliance. TRIAL REGISTRATION NUMBER: This randomised controlled trial has been registered at ClinicalTrials.gov Identifier: NCT04171908.