Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP), a commonly used clinical marker of cardiac function, is associated with the presence of stroke symptoms and is a strong risk factor for future atrial fibrillation, stroke, and all-cause mortality. Few data are available on the association between NT-proBNP levels and stroke recurrence. Objective: We studied the relationship between NT-proBNP and risk of future ischemic stroke across the continuum of preexisting cerebrovascular conditions: asymptomatic, prior stroke symptoms, prior transient ischemic attack (TIA), and prior stroke. Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort enrolled 30,239 black and white Americans aged 45 years and older from 2003 to 2007. With 5.4 years follow-up, baseline NT-proBNP was measured in 892 participants who developed ischemic stroke and a 4328-person cohort random sample. Hazard ratios of stroke by baseline NT-proBNP were calculated in groups based on the presence of prebaseline cerebrovascular conditions. Results: In the fully adjusted model, elevated NT-proBNP was associated with stroke risk in participants without a preexisting cerebrovascular condition (hazard ratio [HR], 2.32; 95% confidence interval [CI], 1.84-2.94) and in participants with a history of stroke symptoms (HR, 1.67; 95% CI, 1.01-2.78) or transient ischemic attack (HR, 2.66; 95% CI, 1.00-7.04) but not among those with prior stroke (HR, 1.26; 95% CI, 0.71-2.21). Conclusions: These findings support the potential for NT-proBNP testing to identify people who are at highest risk for future stroke.