Background: Surgically implanted aortic bio-prostheses are prone to degeneration and eventually failure within 10 to 20 years. Transcatheter aortic valve replacement “valve-in-valve” (TAVR-VIV) is an effective treatment for patients deemed at prohibitive risk for surgical redo. However, Mitroflow, Freedom, Toronto and Freestyle bioprostheses pose a high risk of left main obstruction and are only marginally represented in the available literature. Methods and Results After evaluation of local Heart Team, TAVR-VIV implantation was performed in 20 patients with a failed Mitroflow (8), Freedom (5), Toronto SPV (3), Freestyle (2), Trifecta (1), or Mosaic (1) bioprostheses. Patients/prostheses were divided in type A (mainly stenotic, 8 pts), and type B (mainly regurgitant, 12 pts). All patients were managed protecting the left main ostium. At 30 days, 2 fatalities (10%) and 2 myocardial infarction (10%) occurred. At a mean follow up of 6 months, 2 further fatalities (cumulative survival rate of 80%) were observed (cumulative incidence of 5%). Conclusions This registry specifically focusing on extremely high risk TAVR-VIV is a proof of concept. The protection of the left main during the procedure allows patients initially deemed at highest or even prohibitive risk to be successfully treated and further support the use of bioprostheses at the time of the surgical treatment.