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Background Heart failure (HF) is a growing public health concern with high morbidity and mortality that increase with age. Ketone bodies (KB), acetoacetate and β-hydroxybutyrate, serve as an alternative myocardial energy source, particularly under metabolic stress. KB metabolism can influence haemodynamic parameters, such as improving systolic function, and HF patients show increased KB utilisation. The KB ratio (acetoacetate: β-hydroxybutyrate) reflects mitochondrial redox potential (NAD+/NADH). However, its role in predicting HF incidence has not been previously investigated.Purpose To investigate the association between total KB levels, individual KB components, and KB ratio with incident HF in a population-based cohort of older men from the British Regional Heart Study (BRHS).Methods 3459 men aged 60–79 years without prevalent myocardial infarction (MI) or HF from the prospective BRHS cohort were included in the analysis. KB levels were measured by nuclear magnetic resonance spectroscopy. Participants were followed up for a median 15.9 years. HF incidence was determined via primary care and national health records. Cox proportional hazards models were used to assess associations, adjusting for established cardiovascular risk factors and inflammatory markers.Results 375 participants (10.8%) developed incident HF during follow-up (6.82 cases per 1,000 person-years). Total KB levels were not significantly associated with incident HF (HR 0.88 [0.72–1.08], p=0.231). Review of previous epidemiological cohort studies revealed conflicting findings regarding the association between total/individual KB and incident HF. However, KB ratio was significantly associated with increased HF incidence (HR 2.67 [1.11–6.41], p=0.028). The association was stronger in younger individuals (<70 years) and HF with reduced ejection fraction groups but did not appear to be influenced by diabetic status. Restricted cubic spline analysis demonstrated a linear increase in HF risk beyond a KB ratio of 0.35, suggesting a potential threshold for increased susceptibility. Total KB and KB ratio were not associated with incident MI (Total KB HR 0.86 [0.67–1.09], p=0.213; KB Ratio HR 0.87 [0.68–1.11], p=0.261).Conclusion KB ratio, a marker of mitochondrial redox potential (NAD +/ NADH), is significantly associated with an increased risk of HF incidence independent of established cardiovascular risk factors and inflammatory markers in older adults, particularly in younger individuals and those developing HFrEF. This novel finding suggests that KB ratio may serve as a biomarker of HF incidence and possibly guide risk stratification and potential therapeutic implications targeting mitochondrial metabolism in HF prevention and management.