Background: A significant correlation exists between disability and the volume of black holes (BHL VOL), defined as hypointense lesions on T1-weighted cranial magnetic resonance imaging. A consistent correlation has also been reported between urinary myelin basic protein-like material (MBPLM) and the transition toward secondary progression (SP) from relapsing-remitting (RR) multiple sclerosis (MS). Objective: To improve the management of MS through a noninvasive and cost-effective test for monitoring disease activity or disease status. Design and Methods: From 662 patients with MS (86 with RR MS, 259 with SP MS without continued attacks, and 317 with SP MS with continued attacks), 24-hour urine samples were obtained at enrollment in the phase 3 Linomide (roquinimex) drug study. The urine specimens were analyzed for MBPLM and correlated with clinical features and findings on cranial magnetic resonance imaging. Results: Significant but weak correlations existed between urinary MBPLM and BHL VOL in all patients with MS (r=0.114, P=.003; n=662), patients with SP MS without attacks (r=0.185, P=.003; n= 259), and all patients with SP MS (r=0.122, P=.003; n=576). No significant correlations were detected in the RR MS group or any of the disease groups or subgroups whose Expanded Disability Stares Scale score was 5.0 or lower. In subgroup analysis, the most significant correlation was detected between urinary MBPLM after adjustment for creatinine and BHL VOL in patients with SP MS with an Expanded Disability Status Scale score of 5.5 or higher but without continued relapses (r=0.417, P<.001; n= 138). Conclusions: In patients with advanced SP MS, urinary MBPLM may possibly serve as an indicator of failed remission and axonal damage. Urinary MBPLM correlates with disease status in MS, especially the transition of RR MS to SP MS with advancing disability.