AbstractBackgroundGrowing interest in neuroprotection in transcatheter aortic valve replacement (TAVR) has catalyzed the development of cerebral protection systems (CPS).ObjectivesReport insights from consecutive real‐world patients undergoing TAVR with the Sentinel‐CPS.MethodsPatients with severe aortic stenosis undergoing TAVR from April 2019 to May 2022 were enrolled in a prospective registry. The reason for unsuccessful Sentinel‐CPS deployment and the amount of debris captured by the filters were prospectively recorded.ResultsThe Sentinal CPS was successfully deployed in 330 patients (85%, Group 1). Deployment was not attempted, unsuccessful or only partially successful in 59 patients (15%, Group 2), caused by anatomical factors such as tortuosity, heavy calcification or small dimensions of radial or brachial artery in 46, technical aspects such as puncture failure or dissection in 5 or use of right radial access for the pigtail in 6. Debris was captured in 98% of patients in Group 1. In 40%, the amount of debris was graded moderate or extensive. Predictors for moderate/extensive debris were moderate/severe aortic calcification (OR 1.50, CI 1.05–2.15, p = 0.03), pre‐ and postdilatation (OR 1.97, CI 1.02–3.79, p = 0.04 and OR 1.71, CI 1.01–2.89, p = 0.048). The risk of stroke was numerically lower in patients who underwent TAVR with the Sentinel CPS (2.1 vs. 5.1%, respectively, p = 0.15). There was no stroke during CPS deployment, but one patient had a stroke immediately after device retrieval.ConclusionsThe Sentinel‐CPS was successfully deployed in 85% of patients. Predictors for moderate/extensive debris captured were moderate/severe aortic calcification, pre‐ and postdilatation.