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Measurement of NT-proBNP and copeptin may help identify those at high risk of heart failure (HF). However the value of NT-proBNP and copeptin has been little studied in the older population in primary care. This study aims to examine the use of NT-proBNP and copeptin in improving risk prediction and stratification of HF in older men with and without cardiovascular disease (CVD).This was a prospective study of 3870 men aged 60–79 years with no diagnosed HF followed up for a mean period of 11 years, during which there were 254 incident HF cases. NT-proBNP was associated with HF in those with and without established CVD [diagnosed myocardial infarction (MI), angina, or stroke]. NT-proBNP improved prediction beyond routine conventional risk factors (age, obesity, diabetes, hypertension, history of MI, and history of angina) and the Health ABC Heart Failure Score in all men and in men with and without established CVD (P<0.0001 for improvement in c-statistics). The net reclassification index (NRI) beyond conventional risk factors was 18.8% overall (27.4% for men without CVD and 17.4% for men with CVD). In contrast, copeptin was associated with HF in men with CVD only and did not improve prediction of HF after inclusion of conventional risk factors (P = 0.95 for improvement in c-statistics).NT-proBNP, but not copeptin significantly improves prediction and risk stratification of HF beyond routine clinical parameters obtained in general practice settings in older men both with and without established CVD.