Abstract Introduction: Multiple myeloma (MM) is a rare cancer of the plasma cells. Black men and women are at a greater than 2-fold increased risk of MM as compared to other racial/ethnic groups. In 2021, Black women living in the United States (U.S.) were diagnosed with MM at a rate of 13.9 per 100,000 women, and incidence has increased by more than 30% since 2000. Factors associated with the neighborhood in which Black women live and work may be one area to consider to disentangle this racial disparity in MM incidence and reduce the burden of disease for Black women. Methods: We evaluated the association between two neighborhood-level indices and MM within the Black Women’s Health Study, a longitudinal cohort of 59,000 self- identified Black women ages 21-69 at enrollment in 1995. Participant addresses at baseline were geocoded and linked with U.S. Census Bureau and American Community Survey data. We conducted a factor analysis to a create neighborhood concentrated disadvantage (nDIS) score, which included 6 variables: percentage of individuals below the poverty line, percentage of individuals on public assistance, percentage of female headed households, percentage unemployed, percentage of individuals ≤18 years, and percentage of Black residents. A neighborhood socioeconomic status (nSES) score included median household income, median housing value, percentage of households receiving interest, dividend or net rental income, percentage of adults aged ≥25 years who completed college, percentage of employed persons aged ≥16 years in occupations classified as managerial, executive or professional, and percentage of families with children that are not headed by a single female. We used Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for the association of quartiles of nSES and nDIS in relation to MM risk. Multivariable models were adjusted for age, body mass index, educational attainment, alcohol consumption, physical activity, and cigarette smoking. Results: During follow-up through 2021, we identified 276 incident cases of MM. Multivariable-adjusted HRs were 1.43 (95% CI: 1.00, 2.03) for women living in the highest quartile of neighborhood disadvantage relative to the lowest quartile, and 1.23 (95% CI: 0.86, 1.76) for women living in neighborhoods in the lowest quartiles of nSES compared to the highest. Conclusions: Black women in the U.S. living in neighborhoods of high concentrated disadvantage have an increased risk for MM compared to women who live in more advantaged communities, even after adjustment for individual SES as measured by educational attainment. Future studies to further tease apart specific neighborhood-level factors (e.g., walkability, chronic stress, environmental pollution, opportunities to engage in healthy behaviors) that might influence risk of MM would be beneficial. Ultimately, community reinvestment may offer an opportunity to reduce the increasing burden of MM among Black women. Citation Format: Etienne X. Holder, Julie R. Palmer, Kimberly A. Bertrand. Neighborhood disadvantage and multiple myeloma risk among Black women living in the United States [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A047.