© 2019, American Society for Clinical Investigation. BACKGROUND. Black individuals have lower natriuretic peptide levels and greater risk of heart failure (HF) than White individuals. Higher N-terminal pro–B-type natriuretic peptide (NT-proBNP) is associated with increased risk of incident HF, but little information is available in Black individuals. We examined race-specific differences in (a) the association of NT-proBNP with incident HF and (b) the predictive ability of NT-proBNP for incident HF across BMI and estimated glomerular filtration rate (eGFR) categories. METHODS. In a prospective case-cohort study, baseline NT-proBNP was measured among 687 participants with incident HF and 2923 (weighted 20,075) non-case randomly selected participants. Multivariable Cox proportional hazard modeling was used to assess the objectives of our study. Global Wald χ2 score estimated from multivariable Cox models was used to assess predictive ability of NT-proBNP across BMI and eGFR categories. RESULTS. In the multivariable model, a doubling of NT-proBNP concentration was associated with greater risk of incident HF among White individuals (HR: 1.73; 95% CI: 1.55–1.94) than Black individuals (HR: 1.51; 95% CI: 1.34–1.70), with Pinteraction by race of 0.024. Higher NT-proBNP was the strongest predictor of incident HF across all BMI and eGFR categories among White individuals. In contrast, among Black individuals with obesity (BMI ≥ 30 kg/m2) or eGFR less than 60 mL/min/1.73 m2, the predictive ability of NT-proBNP for incident HF was attenuated. CONCLUSIONS. The magnitude of the association of higher NT-proBNP with incident HF risk was greater among White individuals than Black individuals. The diminished ability of NT-proBNP to predict the risk of HF in the Black population with obesity or impaired kidney function highlights the need for further investigations. FUNDING. National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; National Institute on Aging; and the NIH.