Background: There is continuous debate to the use of biomarkers in the general practitioners office and to what degree the established biomarkers N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and high-sensitive C-reactive protein (hs-CRP) might contribute to improved prediction of incident cardiovascular events. Objective: To evaluate the utility and 5-year predictive value of a single measurement of NT-pro-BNP and hs-CRP for incident cardiovascular events, and its added value beyond the contribution of conventional risk factors in primary care. Methods: Five year prospective longitudinal clinical epidemiological study in a nationwide sample of 4,775 primary care subjects (mean age 55.8 years, 62 % women) without coronary artery disease at baseline. Main outcome measures were incident major cardiovascular events and all-cause death. Results: During the 5 years of follow-up, 188 subjects (3.9 %) died or experienced a first major cardiovascular event. The addition of NT-pro-BNP, but not of hs-CRP to a prediction model with established cardiovascular risk factors improved the prediction of major cardiovascular events (increase in C statistic by 0.009; p = 0.008), and was associated with a significant improvement in net reclassification improvement (NRI = 23.6 %; p = 0.003). Conclusion: In a primary care setting, one single measurement of NT-pro-BNP, but not of hs-CRP significantly improves the prediction of incident cardiovascular events.