Objective: To investigate differences in disability between African American and Caucasian patients with multiple sclerosis (MS) by comparing the relationship between current age and disability between races and by assessing the effect of adjustment for socioeconomic status (SES) on the associations. Methods: The authors selected US participants from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry with an age at symptom onset of 10 to 60 years, who reported their race as Caucasian or African American (n = 21,557). They classified participants as having mild, moderate, or severe disability in the domains of mobility, hand function, cognition, and vision using Patient Determined Disease Steps and Performance Scales and assessed the association of disability with race using polytomous logistic regression. Results: Disability increased more rapidly with increasing disease duration in older patients, but there was no interaction between race and age. African Americans had increased odds of severe vs mild disability in all four domains (odds ratio [OR] [95%CI]: hand 1.35 [1.10 to 1.64]; vision 1.75 [1.37 to 2.27]; cognition 1.32 [1.04 to 1.67]; mobility 1.32 [1.11 to 1.56]). Adjustment for all covariates, including SES, attenuated these associations (OR [95%CI]: hand 1.27 [1.00 to 1.61]; vision 1.59 [1.19 to 2.08]; cognition 0.98 [0.74 to 1.30]; mobility 1.37 [1.11 to 1.67]). Lack of adjustment for SES produced stronger associations. After enrollment in NARCOMS, disability progression did not differ between the groups. Conclusions: African Americans experience greater multiple sclerosis-associated disability than Caucasians. Failure to account for socioeconomic status leads to overestimation of these differences. Disease progression is similar in African Americans and Caucasians after diagnosis. Objective: To investigate differences in disability between African American and Caucasian patients with multiple sclerosis (MS) by comparing the relationship between current age and disability between races and by assessing the effect of adjustment for socioeconomic status (SES) on the associations. Methods: The authors selected US participants from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry with an age at symptom onset of 10 to 60 years, who reported their race as Caucasian or African American (n = 21,557). They classified participants as having mild , moderate, or severe disability in the domains of mobility, hand function, cognition, and vision using Patient Determined Disease Steps and Performance Scales and assessed the association of disability with race using polytomous logistic regression. Results: Disability increased more rapidly with increasing disease duration in older patients, but there was no interaction between race and age. African A mericans had increased odds of severe vs mild disability in all four domains (odds ratio [OR] [95% CI]: hand 1.35 [1.10 to 1.64]; vision 1.75 [1.37 to 2.27]; cognition 1.32 [1.04 to 1.67] 1.32 [1.11 to 1.56]). Adjustment for all covariates, including SES, attenuated these associations (OR [95% CI]: hand 1.27 [1.00 to 1.61]; vision 1.59 [1.19 to 2.08]; cognition 0.98 [0.74 to 1.30] ; mobility 1.37 [1.11 to 1.67]). Lack of adjustment for SES created strong associations. After enrollment in NARCOMS, disability progression did not differ between the groups. Conclusions: African Americans experience greater multiple sclerosis-associated disability than Caucasians. Failure to account for socioeconomic status leads to overestimation of these differences. Disease progression is similar in African Americans and Caucasians after diagnosis.