Abstract Background Transcatheter Aortic Valve Implantation (TAVI) has gained ground in the management of severe aortic stenosis, even in low-surgical risk patients. However, TAVI prostheses, like bioprostheses, have a finite lifetime; thus, TAVI in patients with previous TAVI (TAVI-in-TAVI) rates are radically increased. Although data regarding TAVI indicate low mortality and stroke rates within the first year, TAVI-in-TAVI is less studied. Purpose The aim of the study is to systematically review and summarize available data regarding the safety and the outcomes of TAVI-in-TAVI. Methods This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 10, 2024, for studies assessing the characteristics and outcomes of patients undergoing TAVI-in-TAVI. Primary endpoint of our systematic review and meta-analysis is the in-hospital, 30-days and 1-year mortality rates. Secondary endpoints comprised in-hospital, 30-days and 1-year stroke rates, in-hospital vascular complications, conversion to surgery, coronary compression or obstruction, and perforation with or without tamponade, and in-hospital and 30-days permanent pacemaker implantation (PPM) implantation. Endpoint definitions followed the Valve Academic Research Consortium 3 criteria. The cumulative incidence of primary and secondary endpoints and the corresponding 95% confidence intervals (CI) were estimated. A random effects model (DerSimonian-Laird) was used to account for heterogeneity among the included studies. Results Our meta-analysis included a total of 5 studies and 2,145 patients undergoing TAVI-in-TAVI, 72.9% (N=1,564) of whom were treated with a balloon-expandable valve. Our analysis showed that patients undergoing TAVI-in-TAVI had 3.7% (95% CI: 1.6%-5.9%), 3.9% (95% CI: 3%-4.7%) and 12.5% (95% CI: 11%-14%) in-hospital, 30-days and 1-year all-cause mortality, while stroke occurred in 1.8% (95% CI: 1.2%-2.4%), 2.1% (95% CI: 1.4%-2.9%) and 3% (95% CI: 2.3%-3.8%) of the patients in-hospital, 30-days and 1-year, respectively. Notalby, conversion to surgery, coronary compression/obstruction and perforation with or without tamponade occurred in <1% of the patients, while 6.1% (95% CI: 2.2%-9.9%) of the patients had vascular complications during the procedure. Considering the PPM implantation rates, patients had a 1.8% (95% CI: 1.2%-2.4%) for in-hospital and a 6.8% (95% CI: 5.2%-8.3%) for 30-days incidence. Conclusion Our systematic review and meta-analysis is the first to present that TAVI-in-TAVI has an acceptable safety profile with relatively low in-hospital, 30-days and 1-year mortality and stroke rates, comparable to the native-valve-TAVI. Taking into consideration that TAVI-in-TAVI might be the only therapeutic approach for an increasing number of patients, further studies are warranted to further assess its safety and efficacy and to provide additional procedural techniques.TAVI-in-TAVI mortality rates