Abstract Background Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a suitable manner to prevent hemodynamic deterioration during high-risk percutaneous coronary intervention (PCI). VA-ECMO is mainly surgically deployed under general anaesthesia. New developments now facilitate completely percutaneous insertion of VA-ECMO with only local anaesthesia, reducing operating team size and hospital costs. Purpose The aim of this study is to provide data on the outcomes of completely percutaneous use of VA-ECMO during high-risk PCI with local anaesthesia. Methods A retrospective single-centre registry was performed including all patients undergoing ECMO-assisted high-risk PCI, who were rejected for coronary artery bypass graft (CABG) as primary treatment option. Primary endpoint was the incidence of major adverse cardiac events (MACE), assessed during hospital admission and after discharge up to 90 days. Results Between January 2020 and February 2024, 34 patients undergoing ECMO-assisted high-risk PCI were included. The mean age of the population is 71.9 (± 8.4) and 27 (79.4%) patients are male. The mean left ventricular ejection fraction is 28.5 (± 11.1) percent and complexity indices were high, including STS mortality score: 4.1 (± 2.8), SYNTAX score I: 31.7 (± 9.4), SYNTAX score II: (PCI) 54.8 (± 10.8). Femoral artery was used for cannulation in 30 (88.2%) patients, of which one patient required an additional femoral backflow cannula due to prolonged ECMO support. Local anaesthesia in combination with preprocedural oral benzodiazepine was the preferred choice of anaesthesia (85.3%). Closure was predominantly performed with a percutaneous closure device (97.1%). Successful revascularization and procedural success were achieved in all patients. In-hospital MACE occurred in 2 (6.1%) patients. MACE occurred within 90 days in 5 (20.8%) patients after discharge. Conclusion High-risk PCI with completely percutaneous use of VA-ECMO with local anaesthesia is a novel concept, providing a suitable alternative to the standard surgical use of VA-ECMO with general anaesthesia.