Objectives: The aim of this study was to examine real-world experience with repeat transcatheter aortic valve replacement (TAVR) in a population-based national database., Background: Repeat TAVR is a growing option in patients requiring reintervention for TAVR. However, large-scale studies with longitudinal follow-up are limited., Methods: All Medicare beneficiaries who underwent TAVR from 2012 to 2017 were included. Outcomes included 30-day and longitudinal mortality and major adverse cardiovascular events, defined as death, stroke, pacemaker insertion, major bleeding, acute kidney injury, or cardiac arrest. Outcomes of repeat TAVR were compared with surgical explantation after TAVR (TAVR explantation) in a matched analysis., Results: Of 133,250 patients who underwent TAVR, 617 (0.46%) underwent subsequent repeat TAVR at a median interval of 154 days (interquartile range: 58-537 days). Mortality at 30 days and 1 year was 6.0% and 22.0%, respectively. Rates of 30-day stroke and pacemaker insertion were 1.8% and 4.2%. Mortality at 30 days was lower in those who underwent their first TAVR during the later era (2015-2017) compared with earlier years (2012-2014) (4.6% vs 8.7%; P = 0.049). Repeat TAVR was associated with lower 30-day mortality compared with a matched group undergoing TAVR explantation (6.2% vs 12.3%; P = 0.05), although 1-year mortality was similar (21.0% vs 20.8%; P = 1.000). The incidence of 30-day major adverse cardiovascular events was higher with TAVR explantation compared with repeat TAVR (risk ratio: 2.92; 95% CI: 1.88-4.99; P ≤ 0.001)., Conclusions: Repeat TAVR was performed with acceptable 30-day mortality in this high-risk population. Short-term outcomes were superior to surgical explantation, but 1-year outcomes were similar. Repeat TAVR will likely be an important option for aortic valve reintervention after TAVR., Competing Interests: Funding Support and Author Disclosures This work was supported by Levinger gift funds from Brigham and Women’s Hospital, Harvard Medical School. Dr Kaneko is a speaker for Edwards Lifesciences, Medtronic, Abbott, and Baylis Medical; and is a consultant for 4C Medical. Dr Tang is a physician proctor for Medtronic; and is a consultant for Medtronic, W.L. Gore & Associates, and Abbott Structural Heart. Dr Bapat has served as a consultant for Medtronic, Edwards Lifesciences, 4C Medical, and Boston Scientific. Dr O’Gara has been a consultant to Medtronic and Edwards Lifesciences. Dr Bhatt is an advisory board member for Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, PLx Pharma, and Regado Biosciences; is on the boards of directors of the Boston VA Research Institute, the Society of Cardiovascular Patient Care, and TobeSoft; is chair of the American Heart Association Quality Oversight Committee; is a member of data monitoring committees for the Baim Institute for Clinical Research (formerly the Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), the Cleveland Clinic (including for the ExCEED trial, funded by Edwards Lifesciences), the Duke Clinical Research Institute, the Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo), and the Population Health Research Institute; has received honoraria from the American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; vice chair, ACC Accreditation Committee), the Baim Institute for Clinical Research (formerly the Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor-in-chief, Harvard Heart Letter), the Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor-in-chief, Journal of Invasive Cardiology), the Journal of the American College of Cardiology (guest editor, associate editor), Medtelligence/ReachMD (continuing medical education steering committees), the Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and US national coleader, funded by Bayer), Slack Publications (chief medical editor, Cardiology Today’s Intervention), the Society of Cardiovascular Patient Care (secretary/treasurer), WebMD (continuing medical education steering committees); is deputy editor of Clinical Cardiology; is chair of the National Cardiovascular Data Registry ACTION Registry Steering Committee and the VA CART Research and Publications Committee; has received research funding from Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, PhaseBio, Pfizer, PLx Pharma, Regeneron, Roche, Sanofi, Synaptic, and The Medicines Company; has received royalties from Elsevier (editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); is a site coinvestigator for Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), and Svelte; is a trustee of the American College of Cardiology; and has conducted unfunded research for FlowCo, Merck, Novo Nordisk, and Takeda. Dr Webb has been a consultant to and has received research funding from Edwards Lifesciences, Abbott Vascular, Boston Scientific, and ViVitro Labs. Dr Reardon serves on an advisory board for Medtronic. Dr Thourani receives grant support, paid to his institution, and advisory fees from Edwards Lifesciences, Boston Scientific, Abbott Vascular, and JenaValve Technology; and receives advisory fees from Gore Vascular. Dr Gleason receives institutional grant support from Medtronic but receives no personal income. Dr Shah has received compensation as a proctor for Edwards Lifesciences; and has received educational grants from Edwards Lifesciences, Medtronic, and Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)