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Background: Heyde syndrome is the co-occurrence of aortic stenosis and gastrointestinal bleeding secondary to angiodysplasias. Surgical aortic valve replacement effectively reduces bleeding, but the effects of transcatheter aortic valve implantation (TAVI) are largely unknown. This study aimed to describe the reduction of gastrointestinal bleeding in patients with Heyde syndrome after TAVI and to identify the factors associated with rebleeding. Methods: We enrolled patients with Heyde syndrome from a prospective TAVI registry. Gastrointestinal bleeding episodes were assessed by the Bleeding Academic Research Consortium classification, and cumulative incidence functions were used to calculate cessation rates. Factors potentially associated with rebleeding were analyzed using logistic regression. Differences between Heyde and non-Heyde patients were assessed through a case-cohort study. Results: Between December 2008 and June 2020, 1111 patients underwent TAVI. There were 70 patients with Heyde syndrome (6.3%). In the first year following TAVI, gastrointestinal bleeding ceased in 46 of 70 patients (62% [95% CI, 50%–74%]). Bleeding episodes decreased from 3.2 (95% CI, 2.5–4.2) to 1.6 ([95% CI, 1.2–2.2] P =0.001) and hemoglobin levels increased from 10.3 (95% CI, 10.0–10.8) to 11.3 (95% CI, 10.8–11.6) g/dL (P =0.007). Between 1 and 5 years after TAVI (35 [interquartile range, 21–51] months), 53 of 62 patients (83% [95% CI, 72%–92%]) no longer experienced gastrointestinal bleeding. Paravalvular leakage (≥mild) was associated with rebleeding risk (odds ratio, 3.65 [95% CI, 1.36–9.80]; P =0.010). Periprocedural bleeding was more common in Heyde than in control patients (adjusted odds ratio, 2.55 [95% CI, 1.37–4.73]; P =0.003). Conclusions: Patients with Heyde syndrome are at increased risk for periprocedural bleeding. Post-TAVI, gastrointestinal bleeding disappears in the majority of patients. Paravalvular leakage may curtail these clinical benefits. [ABSTRACT FROM AUTHOR]