IntroductionTranscatheter mitral valve‐in‐valve replacement (TMVR ViV) is becoming a favorable, less invasive procedure among high‐risk patients to manage mitral valve dysfunction. We aimed to investigate the trends of the predictors and outcomes of the procedure.MethodsThe national inpatient sample databases of 2016−2020 were analyzed using STATA 17 software and ICD‐10 codes for TMVR ViV, with stratification for mitral stenosis (MS) or Mitral regurgitation (MR) as etiology for prosthetic valve dysfunction. The primary outcome was inpatient mortality, whereas myocardial infarction and stroke were secondary outcomes.ResultsOver the 5 years, a total of 5233 patients with TMVR ViV were found, exhibiting a yearly increase of procedural volume from 490 in 2016 to 1400 patients in 2020 and decreasing odds for inpatient mortality (aOR 0.74, p = 0.53 in 2017 to aOR: 0.33, p < 0.04 in 2020). Myocardial infarction was significantly lower with TMVR ViV over the years and with similar odds of stroke post‐operatively. There was a decreasing trend of length of stay over the years. Upon stratification, 635 patients were found to have MR with a prosthetic valve (MRPV), and 50 had MS with a prosthetic valve (MSPV). Among those who underwent TMVR ViV, in‐hospital mortality was recorded in 30 (4%) patients of MRPV and 15 (30%) patients of MSPV (p = 0.002), with significantly higher odds for the MSPV group than MRPV.ConclusionThe continued decline in short‐term mortality and length of stay, with the progressive incorporation of more patients, gives real‐world evidence for the safety and efficacy of TMVR ViV. Extended post‐procedure follow‐up studies are required to investigate long‐term procedural benefits and to explore factors causing higher mortality in the MSPV population.