Background— Measurement of B-type natriuretic peptide (BNP) concentration or its precursor (N-terminal fragment [NT-proBNP]) is recommended in patients with symptoms of left ventricular dysfunction and in other settings, but the relevance of these peptides to cardiovascular disease (CVD) in general populations or in patients with stable vascular disease is uncertain. Methods and Results— Data were collated from 40 long-term prospective studies involving a total of 87 474 participants and 10 625 incident CVD outcomes. In a comparison of individuals in the top third with those in the bottom third of baseline values of natriuretic peptides, the combined risk ratio (RR), adjusted for several conventional risk factors, was 2.82 (95% confidence interval [CI], 2.40 to 3.33) for CVD. Analysis of the 6 studies with at least 250 CVD outcomes (which should be less prone to selective reporting than are smaller studies) yielded an adjusted RR of 1.94 (95% CI, 1.57 to 2.39). RRs were broadly similar with BNP or NT-proBNP (RR, 2.89 [95% CI, 1.91 to 4.38] and 2.82 [95% CI, 2.35 to 3.38], respectively) and by different baseline vascular risk (RR, 2.68 [95% CI, 2.07 to 3.47] in approximately general populations; RR, 3.35 [95% CI, 2.38 to 4.72] in people with elevated vascular risk factors; RR, 2.60 [95% CI, 1.99 to 3.38] in patients with stable CVD). Assay of BNP or NT-proBNP in addition to measurement of conventional CVD risk factors yielded generally modest improvements in risk discrimination. Conclusions— Available prospective studies indicate strong associations between circulating concentration of natriuretic peptides and CVD risk under a range of different circumstances. Further investigation is warranted, particularly in large general population studies, to clarify any predictive utility of these markers and to better control for publication bias.