Highlights • AVS is associated with a high prevalence and large spectrum of CHIP-driver variants. • Patients carrying TET2 mutations with low VAF (2%-10%) have a decreased overall 5-year survival after TAVR. • These findings could provide a novel tool for prognosis assessment in patients with severe AVS undergoing TAVR. • Future functional studies in relevant preclinical models are needed to investigate the mechanisms by which CHIP-driver variants contribute to AVS and impact the clinical prognosis after TAVR, especially in TET2. Summary Clonal hematopoiesis of indeterminate potential (CHIP) is considered as being a novel age-related risk factor for cardiovascular diseases. By capture-sequencing of a 67-gene panel, we established a large spectrum of CHIP in 258 patients with aortic valve stenosis undergoing transcatheter aortic valve replacement (TAVR) and assessed their association with long-term survival after TAVR. One or several CHIP variants in 35 genes were identified in 68% of the cohort, DNMT3A and TET2 being the 2 most frequently mutated genes. Patients carrying a TET2-CHIP-driver variant with low variant allele frequency (2%-10%) had a significant decrease in overall survival 5 years after TAVR. Visual Abstract