Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) is associated with an increased risk of heart failure (HF) and stroke, particularly HF with preserved ejection fraction and hemorrhagic stroke (HS).Hypothesis: We hypothesized that CHIP is associated with incident hypertension and this association mediates the effect of CHIP on HF and HS.Methods: In 200K UK-Biobank participants with exome sequencing, we ascertained CHIP as variant allele fraction (VAF) ≥2% and large CHIP as VAF ≥10%. Hypertension, HF, and HS diagnosis were determined based on the ICD-9 and ICD-10 codes. Cox proportional hazards models were used to test the association of both CHIP and the CHIP subtypes based on the most implicated driver genes (i.e., DNMT3A, TET2, and ASXL1) with incident hypertension. Logistic regression models were used for mediation analyses, quantifying the extent to which hypertension mediates the effects of CHIP.Results: After excluding those with hematological malignancy (n=1,025) and pre-existing hypertension (n=14,754), 184,760 participants (56.14±8.12 years, 44.25% male, and 95.33% white ethnicity) were included. During a median follow-up of 12.2 years, 42,049 (22.76%) participants developed hypertension. CHIP mutations were significantly associated with incident hypertension (Table). Mutations in DNMT3A and TET2 but not ASXL1 drove this association. Mediation analysis revealed 17.9% (9.4% - 38.2%, P<0.001) of the effect of CHIP on HF and 5.7% (2.4% - 22.4%, P<0.001) of the effect on HS were mediated through the increased risk of hypertension.Conclusion: CHIP is associated with an increased risk of hypertension. The association of CHIP with HF and HS is partially mediated by hypertension. These findings suggest a new mechanistic pathway for the association of CHIP with cardiovascular diseases.