Importance: Sex- and race-based differences in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are poorly understood. Clinical decisions are often informed by absolute - as opposed to relative - risk, but absolute risk of incident heart failure (HF) associated with NT-proBNP concentration across these important demographic categories is unclear. Objective: To determine whether physiologic determinants of NT-proBNP concentrations account for sex and race differences, and to more uniformly predict HF risk using NT-proBNP in these demographic subgroups. Design, Setting, and Participants: In the longitudinal Atherosclerosis Risk in Communities epidemiologic prospective community-based cohort study, the association of NT-proBNP concentration with relative and absolute risk of HF by sex- and race-based categories was assessed at study visit 2 (1990-1992) and study visit 5 (2011-2013) using Cox and Poisson regression. These data were analyzed from June 2018 to October 2021. The contribution of clinical, anthropometric, echocardiographic, and laboratory parameters to sex- and race-based differences in NT-proBNP concentration was assessed at visit 5 using linear regression. Participants included were free of HF in midlife (visit 2; a total of 12750 participants) and late life (visit 5; a total of 5191 participants). Exposures: NT-proBNP concentration. Main Outcomes and Measures: Incident HF or death. Results: Among the 5191 HF-free participants at visit 5, the mean (SD) age was 76.0 (5.2) years, 2104 (41%) were male, 1043 (20%) were Black, and the median (IQR) NT-proBNP concentration was 124 (64-239) pg/. In both midlife and late life, NT-proBNP concentration was lowest in Black men (median [IQR] concentration: visit 2, 30 [14-67] pg/mL; visit 5, 74 [34-153] pg/mL) and highest in White women (median [IQR] concentration: visit 2, 70 [42-111] pg/mL; visit, 5, 154 [82-268] pg/mL). Sex and race differences in NT-proBNP concentration persisted after accounting for age, income, education, area deprivation index, cardiovascular diseases, left ventricular structure (LV), LV function, LV wall stress, weight and fat mass, and estimated glomerular filtration rate. Substantial differences in the absolute risk of incident HF or death existed across the sex- and race-based categories at any NT-proBNP concentration (eg, 7-fold [rate ratio, 6.7; 95% CI, 4.6-9.9] and 3-fold [rate ratio, 2.7; 95% CI, 1.7-4.1] difference at visit 2 and visit 5, respectively, at guideline-recommended thresholds) with higher risk consistently observed among Black men and lower risk in White women. Results were replicated in a cohort of participants from the Cardiovascular Health Study. Conclusions and Relevance: In this study, sex- and race-based differences in NT-proBNP persisted after accounting for known physiologic determinants. Absolute risk associated with a given value of NT-proBNP varied substantially by sex and race. Consideration of NT-proBNP values in the context of sex and race allows for more uniform prediction of absolute risk across important demographic subgroups..