Introduction Early spinal cord (SC) lesions in patients with relapsing-remitting MS (RRMS) are associated with an increased risk of disability in the medium term. However, accurate quantification of these lesions on conventional MRI is difficult and imperfectly reflects the severity of SC damage. In this study, we assessed the added value of different metrics extracted from quantitative spinal cord MRI and reflecting microstructure to predict patient disability at 5 years. Objectives To assess the relationship between baseline SC fractional anisotropy (FA) and magnetization transfer ratio (MTR), the occurrence of atrophy and disability at 5-year in early RRMS patients and their added value compared to initial brain and SC lesion load. Methods After IRB approval (NCT02117375), 76 RRMS patients (disease duration <1 year; mean EDSS=0.78) were included in a multicenter study and scanned at baseline and 5 years. For each subject, we measured 1) SC microstructural damage using magnetization transfer ratio (MTR) and DTI fractional anisotropy (FA) averaged over C4C6; 2) SC atrophy using cross sectional area (CSA) averaged over C2C3; 3) SC lesion load manually segmented on axial cervical T2*w; 4) brain lesion load automatically segmented on 3D FLAIR. Partial correlations between each quantitative metric and disability score or atrophy measurement at 5-year were calculated, with age and gender, and in a second model with SC lesion load as additional covariates. Results The 5-year EDSS was associated with the baseline SC lesion load (r=.29, p=.049), but not with the brain lesion load. The 5-year pyramidal sub-score was not associated with either cervical or brain lesion load. Concerning the microstructural components, both the baseline SC FA and MTR values were associated with the EDSS (r=-.32, p=.02; r=-.31, p=.04, resp.) and the pyramidal sub-score at 5-year (r=-.38, p=.01; r=-.42, p=.005, resp.). These associations were confirmed independently of cervical lesion load for cervical FA value and 5-year EDSS and for FA and MTR values and 5-year pyramidal sub-score. By contrast, we found no significant association between initial brain or SC lesion load or initial microstructural damage and evolution of CSA at 5-year. Conclusion We highlighted the dominant role of initial SC involvement in the subsequent development of disability in early RRMS patients. In particular, initial spinal cord MTR and FA values may offer a reliable complement to lesion volume, able to capture lesion severity and non focal structural changes in this key structure.