Purpose <p>Predicting long-term outcomes after transcatheter aortic valve implantation (TAVI) remains challenging. Recent studies have indicated the potential of intraoperative cerebral regional oxygen saturation (rScO₂) in estimating long-term outcomes after cardiac surgery. This study aimed to investigate the association between long-term outcomes after TAVI and pre-operative, procedural, and anesthesia-related factors, including rScO₂.</p> Methods <p>We conducted a retrospective observational cohort study of 301 consecutive patients who underwent TAVI under monitored anesthesia care at our institution between April 2017 and March 2019. The associations between pre-operative, procedural, and anesthesia-related factors and the 1- and 3-year mortality rates were investigated.</p> Results <p>Of the 301 patients analyzed, 298 were followed-up for 3&#xa0;years. The all-cause mortality rates at 1 and 3&#xa0;years were 6.7% and 20.5%, respectively. Multivariate Cox proportional hazards regression analysis revealed that pre-operative lung vital capacity and post-anesthetic rScO₂ were independent predictors of both 1- and 3-year mortality. Receiver operating characteristic analysis indicated that the cutoff values of post-anesthetic rScO₂ for predicting 1- and 3-year mortality were 55.25 and 57.75, respectively. Multivariate linear regression analysis showed that pre-operative hemoglobin concentration, estimated glomerular filtration rate, serum brain natriuretic hormone level, hypotension at the end of the procedure, and duration of anesthesia were associated with post-anesthetic rScO₂.</p> Conclusion <p>Post-anesthetic rScO₂ was significantly associated with long-term mortality after TAVI.</p>