For a study, researchers sought to see if physiologic drivers of N-terminal pro–B-type natriuretic peptide (NT-proBNP) concentrations account for sex and race disparities in NT-proBNP concentrations and to use NT-proBNP to predict HF risk more uniformly in these demographic categories. At visit 5, the mean (SD) age of the 5,191 HF-free subjects was 76.0 (5.2) years, 2,104 (41%) were male, 1,043 (20%) were Black, and the median (IQR) NT-proBNP concentration was 124 (64-239) pg/. NT-proBNP concentrations were lowest in Black males (median [IQR] concentration: visit 2, 30 [14-67] pg/mL; visit 5, 74 [34-153] pg/mL) and greatest in White women (median [IQR] concentration: visit 2, 70 [42-111] pg/mL; visit 5, 154 [82-268] pg/mL) in both midlife and late-life. After controlling for age, income, education, area deprivation index, cardiovascular illnesses, left ventricular structure (LV), LV function, LV wall stress, weight, and fat mass, and estimated glomerular filtration rate, NT-proBNP concentration variations persisted. At any NT-proBNP concentration, there were significant differences in the absolute risk of incident HF or death across the sex and race-based categories (e.g., a 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 a higher risk in Black men and lower risk in White women. The results were observed in a cohort of Cardiovascular Health Study participants. After accounting for established physiologic factors, sex and race-based variations in NT-proBNP persisted in the investigation. The absolute risk associated with a specific NT-proBNP score varied significantly by sex and race. The use of NT-proBNP values in the context of sex and race allows for more consistent absolute risk prediction across significant demographic categories.