We explored the sensitivity of a novel diffusion MRI method i.e. “Neurite orientation dispersion and density imaging”, to detect and characterize brain microstructure alterations in relapsing-remitting multiple sclerosis patients that we followed up over 2 years. Cross-sectionally, NODDI revealed that an increase in orientation dispersion and a decrease in neurite density in NAWM and in lesions of RRMS patients compared to healthy subjects. Longitudinally, NODDI measured a decreased dispersion and an increased neurite density in MS lesions at 2 years follow-up. Also, NODDI metrics at baseline were highly related to cognition at both baseline and follow-up.