Background: In the last decade, many electronic health (eHealth) technologies have found their way to the field of multiple sclerosis (MS). As people with MS (PwMS) are faced with a disease that fluctuates heavily over time and often have difficulties visiting care centers, there is an immense potential for tele-monitoring solutions to improve both access to and quality of healthcare services. Objectives: To develop a tele-monitoring tool that allows PwMS to follow-up on their disease in collaboration with their care team. The goal of icompanion is to provide PwMS with insights into the fluctuations of their disease while empowering them to take up a more active role in the management of their disease. For the MS care team, icompanion provides quantitative insights into the evolution of their patients’ disease through clinical and subclinical measurements with the goal of allowing more informed clinical decisions to be made. Methods: We organised multiple focus groups with PwMS, MS nurses and neurologists to define their needs and priorities. Based on this input, we developed a mobile app and web portal for PwMS, and a web portal for healthcare professionals (HCPs). Results: Using the icompanion mobile app and web portal, PwMS can monitor their symptoms, physical disability, fatigue and cognition using clinically validated patient-reported outcomes (PROs) like the SymptoMScreen, webEDSS, and NeuroQoL Cognitive Function and Fatigue. In addition, PwMS can keep a diary, log their treatments and set reminders, upload and view their MR images on their smartphone and learn about their disease in a knowledge center. The HCP portal allows MS care teams to monitor the health of their patients using both clinical information (PROs) as subclinical information, namely quantitative brain volumetric measurements extracted from magnetic resonance (MR) images using icobrain. Since its launch in May 2020, over 2357 persons with MS worldwide have used icompanion to monitor their disease (59.1% EU) and have completed more than 2097 Neuro-QoL and 12820 SymptoMScreen PROs. Conclusions: icompanion is a medical device compliant to applicable regulations (Europe: class IIa, US: class I) that allows PwMS to track and gain insight into their disease, helping them take up a more active role in the management of their disease. By sharing their icompanion data, PwMS can provide their clinical team with a more complete picture of the progression of their disease based on both clinical and subclinical measurements, ultimately allowing more informed clinical decisions to be made. Technological advancements like icompanion are an answer to the growing demand for more patient involvement and more data-driven clinical decisions in the care of PwMS.