Patients with severe calcific aortic stenosis are occasionally not amenable to surgery because of advanced age or severe co-morbidities. Percutaneous aortic valve dilation is used but has only limited time relief. While preclinical evidence on percutaneous aortic valve replacement seems promising, only very limited clinical data are available worldwide. We hereby present the first case of percutaneous aortic valve replacement successfully performed in Italy in a 74-year-old high-risk female. This case emphasizes the technical challenges inherent to this procedure and its promising role in selected very high-risk patients with severe aortic stenosis, notwithstanding the early and long-term risk of adverse events.