ABSTRACTObjectiveThe cervical spinal cord (cSC) is highly relevant to clinical dysfunction in multiple sclerosis (MS) but remains understudied using quantitative magnetic resonance imaging (MRI). We assessed magnetization transfer ratio (MTR), a semi‐quantitative MRI measure sensitive to MS‐related tissue microstructural changes, in the cSC and its relationship with clinical outcomes in radiologically isolated syndrome (RIS) and MS.MethodsMTR data were acquired from 52 RIS, 201 relapsing–remitting MS (RRMS), 47 primary progressive MS (PPMS), and 43 control (CON) participants across four sites in the Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo) using 3.0 T MRI systems. Mean MTR was compared between groups in whole cSC and sub‐regions between C2‐C4. Multiple linear regression was used to evaluate relationships between MTR and clinical outcomes, including the expanded disability status scale (EDSS), walking speed test (WST), and manual dexterity test (MDT).ResultsThere were consistent group differences in MTR, which were most pronounced between PPMS and CON (−5.8% to −3.7%, p ≤ 0.01). In PPMS, lower MTR was associated with greater disability as measured by EDSS (β = −0.3 to −0.1, p ≤ 0.03), WST (β = −0.9 to −0.5, p ≤ 0.04), and MDT (β = −0.6 and − 0.5, p = 0.04). In RRMS, MTR was associated with only EDSS (β = −0.1, p ≤ 0.03).InterpretationIn this large sample of RIS and MS, cSC MTR was lowest in PPMS, with associations between MTR and clinical outcomes in MS but not RIS. These findings suggest that MTR provides important information about the underlying tissue microstructural integrity of the cSC relevant to clinical disability in established MS.