Background: Limited data on baseline (BL) characteristics and disease severity exist for Black/African American (AA) patients with multiple sclerosis. Preliminary research suggests that AA patients may have greater BL disease severity and may experience more adverse events (AEs) on treatment than the overall population. The Plegridy Observational Program (POP) explores the real-world safety and effectiveness of peginterferon beta-1a. Objectives: Describe BL characteristics, AEs, and disease activity in AA and nonBlack/African American (NAA) patients from North America enrolled in POP. Methods: POP is fully enrolled and ongoing in approximately 130 sites across 14 countries. Based on the availability of data on race, this analysis includes data only from patients in North America. Data reflect the fourth interim data cut as of September 2019. Data from the fifth interim data cut will be presented. Results: Analyses included 44 AA and 391 NAA patients. BL characteristics were similar between the 2 groups, yet a greater proportion of AA than NAA patients had a family history of cardiac disease (52% vs 31%). In POP, a greater percentage of AA than NAA patients experienced treatment-emergent AEs (73% vs 62%) or serious AEs (SAEs; 16% vs 7%), but no cardiac SAEs were reported in AA patients. Compared to NAA patients, AA patients had a higher incidence of injection site reactions (48% vs 40%), with notable differences in injection site pruritus, pain, and dryness, and a higher incidence of flu-like symptoms (46% vs 40%), with notable differences in chills and myalgia. A greater proportion of AA than NAA patients experienced AEs leading to treatment discontinuation (34% vs 23%), with key differences in the incidence of influenza-like illness, injection site erythema, lymphopenia and leukopenia leading to treatment discontinuation. At 4 years, the proportion of relapse-free patients was high in both subgroups (77% vs 81%). Annualized relapse rates did not differ between the groups (adjusted rate ratio [95% confidence interval]: 1.0271 [0.58, 1.82]; P=0.9268). Conclusions: AA and NAA patients had similar BL characteristics and disease activity. Key differences were observed in their safety profiles, and AA patients were more likely to discontinue peginterferon beta-1a due to AEs than NAA patients. These results help to characterize the experience of AA patients in a real-world setting and may inform health care providers on safety considerations in this population.