This study investigates the association between clonal hematopoiesis of indeterminate potential (CHIP) and incident heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). The study included participants from two racially diverse cohorts: the Jackson Heart Study (JHS) and the Women's Health Initiative (WHI). Whole-genome sequencing was used to identify CHIP, and HF events were adjudicated based on imaging data. The main outcomes were incident HFpEF and HFrEF. The results showed that TET2 CHIP was significantly associated with a 2.4-fold higher risk of HFpEF, independent of traditional cardiovascular risk factors and coronary artery disease (CAD). However, there were no significant associations of any CHIP with HFrEF. Additionally, TET2 CHIP carriers with higher C-reactive protein (CRP) levels had an increased risk of HFpEF. These findings suggest that TET2 CHIP is a novel risk factor for HFpEF and may have implications for the prevention and management of this condition.This study investigates the association between clonal hematopoiesis of indeterminate potential (CHIP) and incident heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). The study included participants from two racially diverse cohorts: the Jackson Heart Study (JHS) and the Women's Health Initiative (WHI). Whole-genome sequencing was used to identify CHIP, and HF events were adjudicated based on imaging data. The main outcomes were incident HFpEF and HFrEF. The results showed that TET2 CHIP was significantly associated with a 2.4-fold higher risk of HFpEF, independent of traditional cardiovascular risk factors and coronary artery disease (CAD). However, there were no significant associations of any CHIP with HFrEF. Additionally, TET2 CHIP carriers with higher C-reactive protein (CRP) levels had an increased risk of HFpEF. These findings suggest that TET2 CHIP is a novel risk factor for HFpEF and may have implications for the prevention and management of this condition.