Background: Acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) is frequent and is associated with adverse outcomes. Past studies have attributed AKI to impaired kidney function at baseline, amount of contrast medium used, major bleeding, and hemodynamic instability during the procedure. Because major bleeding might play a role in the development of AKI, we analyzed the relationship between periprocedural bleeding and the development of AKI and assessed the impact of these 2 important procedure-related complications on outcome. Methods: Consecutive patients undergoing transfemoral TAVI for severe aortic stenosis were prospectively recruited. AKI and bleeding events during hospitalization were recorded, defined, and classified according to the Valve Academic Research Consortium 2 definitions. Logistic and Cox regression was used for predictor and survival analyses. Results: We recruited 422 consecutive patients who underwent TAVI; the mean follow-up duration was 576 ± 400 days. AKI occurred in 66 (15.6%) patients. No patient required dialysis. Fifty patients (12%) had major or life-threatening bleeding. Periprocedural major or life-threatening bleeding was a strong predictor of the development of AKI (odds ratio, 3.19; 95% confidence interval [CI], 1.38-7.1; P= 0.006). Major bleeding was a strong independent predictor for both 30-day and long-term mortality (hazard ratio [HR], 6.67; 95% CI, 2.2-19.8; P= 0.001 and HR, 3.3, 95% CI, 1.2-9.0; P= 0.02, respectively), whereas AKI was not independently associated with increased mortality after TAVI. Conclusions: In patients undergoing transfemoral TAVI, periprocedural bleeding is a strong risk factor for the development of AKI and a major determinant of short- and long-term mortality.