Background We sought to determine the prevalence of pseudobulbar affect (PBA) in a large MS population and assess its association with disability and symptom severity. Methods North American Research Committee on MS (NARCOMS) registry participants completed the Center for Neurologic Study-Lability Scale (CNS-LS), a validated 7- question self-report measure of PBA. A composite PBA score was derived from the sum of responses to the 7 questions. We categorized individuals as PBA-positive (PBA[+]) if they had a composite score ≥17 without current depression. Participants also reported their demographic characteristics and their clinical characteristics using Patient-Determined Disease Steps and Performance Scales. We compared clinical and disease characteristics for PBA(+) responders with those without PBA using descriptive statistics and multivariable multinomial logistic regression. Results Of the 8,136 responders, 574 (7%) had scores ≥17 on the CNS-LS; however, only 200 (2.5%) individuals had scores ≥17 without comorbid depression, of whom only 22 (11%) reported a diagnosis of PBA. PBA(+) individuals tended to be younger (mean [SD] 53.4 [11.0] vs 57.2 [10.3] years), non-white (13% vs 9%), and have lower socioeconomic status (≤$30,000 annual income: 28% vs 22%). In multivariable models, PBA(+) was associated with increased odds of more severe cognitive impairment (moderate vs mild disability OR: 1.37; 95% CI: 1.01, 1.84). Conclusions Our findings suggest that the prevalence of PBA in MS is low, but similar symptoms may cooccur or overlap with depression, highlighting the importance of concomitant assessment of mood when evaluating potential PBA. PBA may be associated with cognitive impairment in people with MS.