Patients with pure native aortic valve regurgitation (NAVR) and increased surgical risk are often denied surgery. This retrospective study aimed to evaluate the "off-label" use of transcatheter heart valves (THV) for the treatment of NAVR. A total of 254 high surgical risk patients with NAVR (age 74 ± 12 years, Society of Thoracic Surgeons risk score 6.6 ± 6.2%) underwent transcatheter aortic valve implantation (TAVI) with early generation (43%) or newer generation (57%) devices at 46 different sites. Device success was significantly higher in patients treated with newer as compared with early generation THV (82% vs 47%, p <0.001). The difference was driven by lower rates of device malpositioning (9% vs 33%) and aortic regurgitation (AR) ≥ moderate (4% vs 31%) and translated into higher clinical efficacy at 30 days in patients treated with newer as compared with early generation THV (72% vs 56%, p = 0.041). Both THV under- and oversizing were associated with an increased risk of THV malpositioning. In conclusion, TAVI is a feasible treatment strategy in selected high-risk patients with NAVR but is associated with a considerable risk of THV malpositioning and residual AR. Although newer-generation THV are associated with better outcomes, novel devices for the treatment of NAVR are warranted.