Background: Performing routine brain magnetic resonance imaging (MRI) is widely accepted as the standard of care for disease monitoring in multiple sclerosis (MS), but the utility of performing routine spinal cord (SC) MRI for this purpose is still debatable., Objective: This study aimed to measure the frequency of new isolated cervical spinal cord lesions (CSLs) in people with MS (pwMS) undergoing routine brain and cervical SC-MRI for disease monitoring and determine the factors associated with the development of new CSLs and their prognostic value., Methods: We retrospectively identified 1576 pwMS who underwent follow-up 3T brain and cervical SC-MRI over a 9-month period. MRI was reviewed for the presence of new brain lesions (BLs) and CSLs. Clinical records were reviewed for interval relapses between sequential scans and subsequent clinical relapse and disability worsening after the follow-up MRI., Results: In 1285 pwMS (median interval: 13-14 months) who were clinically stable with respect to relapses, 73 (5.7%) had new CSLs, of which 49 (3.8%) had concomitant new BLs and 24 (1.9%) had new isolated CSLs only. New asymptomatic CSLs were associated with ⩾ 3 prior relapses ( p = 0.04), no disease-modifying therapy (DMT) use ( p = 0.048), and ⩾ 3 new BLs ( p < 0.001); ⩾ 3 new BLs (OR: 7.11, 95% CI: 4.3-11.7, p < 0.001) remained independently associated with new CSLs on multivariable analysis. Having new asymptomatic CSLs was not independently associated with subsequent relapse or disability worsening after the follow-up MRI (median follow-up time of 26 months)., Conclusion: Routine brain and cervical SC-MRI detected new isolated CSLs in only < 2% of clinically stable pwMS. Developing new asymptomatic CSLs was associated with concomitant new BLs and did not confer an independent increased risk of relapse or disability worsening. Performing SC-MRI may not be warranted for routine monitoring in most pwMS, and performing only brain MRI may be sufficient to capture the vast majority of clinically silent disease activity., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: T.R.U.L., S.P.K., S.S., A.I.E., A.J., and A.W.L. have nothing to disclose. J.O. holds the Waugh Family Chair in MS Research; has received research funding from the MS Society of Canada, the National MS Society, National Institutes of Health (NIH), Brain Canada, the Barford/Love MS Fund of St. Michael’s Hospital, Biogen Idec, Roche, and EMD Serono; and has received compensation for consulting or speaking from EMD Serono, Sanofi Genzyme, Biogen Idec, Novartis, Bristol Myers Squibb (BMS), and Roche. A.B. has received compensation for consulting or speaking from Roche and Novartis.