Background Disabled multiple sclerosis (MS) patients often need intervention of multiple specialists, resulting in a complex organization of care. How this multidisciplinary care should be organized and structured has not been studied. Objective The objective of this article is to address the effectiveness of an integrated multidisciplinary approach versus usual care in MS patients. Methods This is a prospective, randomized, controlled, monocentric clinical trial in MS patients. Two treatment strategies were compared: (i) an integrated multidisciplinary (IMD) approach, consisting of a half-day individually tailored comprehensive assessment in the MS clinic; and (ii) a standard care. The primary outcome was the impact of the strategy on quality of life (QoL) measured using the MSIS-29 scale at inclusion and after six months. Results Fifty MS patients were included. Median MSIS 29 score decreased over six months in the control group (−4.89) and increased in the IMD group (+2.00), with a significant difference between the two groups (p = 0.03). However, in the multivariate analysis, after adjustment of HAD-D and INTERMED score, this difference was no longer significant. Conclusions This prospective, randomized study is the first attempt to evaluate the multidisciplinary approach in MS patients. The results show that, contrary to our expectations, an integrated multidisciplinary approach is not superior to usual care on QoL.