OBJECTIVES: A Multiple Sclerosis (MS) relapse refers to an episode of neurological disturbance during which an acute worsening of function occurs, usually lasting for several days or weeks. The TRIBUNE study provides a detailed exploration of costs and quality of life (QoL) associated with MS relapses. METHODS: Patients in five European countries (France, Germany, Italy, Spain, and United Kingdom) completed a self-administered web-based questionnaire capturing information on demographics, disease characteristics and severity (EDSS), co-morbidities, relapses, resource consumption, and relevant aspects of QoL. The effect of relapses on the socioeconomic burden was assessed by the difference in costs and QoL incurred by relapsing-remitting MS (RRMS) patients with and without relapse(s) with EDSS score ≤5. RESULTS: Out of 1261 patients that completed the questionnaire, 68% had RRMS and 87% reported receiving MS treatment. Nearly half (48%) of the RRMS patients with an EDSS score ≤ 5 reported having at least one relapse during the past year.  This sub-group reported a higher consumption of direct medical resources, professional and informal care, and more sick-leave days compared to patients without relapse(s). The difference in costs of patients with relapse(s) compared to those without ranged between €3,321 and €9,430 across countries. Relapses requiring treatment with steroids or hospitalization resulted in higher costs compared with relapses not needing an intervention; €4,062 - €10,589 versus €340 - €5,096 respectively across countries. QoL outcomes were also correlated with relapse(s). CONCLUSIONS: The additional burden imposed by relapses is important both in terms of excess cost and the impact on quality of life. The use of effective treatments that reduce the frequency of relapses, in addition to providing clinical benefits, could potentially lessen the clinical and socioeconomic burden of MS.