Abstract Background Nowadays use of the Impella for high–risk percutaneous coronary intervention (PCI) is increasing worldwide. The aim of this study is to evaluate in–hospital and long–term outcomes of patients treated for high–risk PCI with the use of Impella CP device. Methods This is a single center registry, which enrolled all consecutive patients treated at Cannizzaro Hospital for high–risk PCI with the use of Impella CP. Data were prospectively entered into a dedicated database. Results From January 2019 to December 2021, 16 patients were enrolled of which 75% were male. The clinical presentation at admission was an acute coronary syndrome in 87.5% of cases (myocardial infarction in 13 patients, unstable angina in 1 subject). The mean left ventricular ejection fraction at admission was 35 ± 7.6%. Ten subjects (62.5%) had diabetes treated with insulin in 90% of cases. The Syntax score was 29 ± 12.3 and the mortality STS score was 8.1 ± 10.4. Left main disease involved 8 (50%) patients, whereas a 3–vessels disease was present in 56% of cases. In most cases –14 (87.5%) patients– the Impella CP was introduced through the femoral artery with percutaneous access, whilst only in 2 (12.5%) subjects a surgical access was necessary. An anatomical complete revascularization was performed in 7 (43.8%) patients. For a total of 2 ± 1 vessels treated for patient and 3 ± 1.3 lesions undergoing PCI, 3 ± 1.8 stent were implanted with a mean total stent length of 81 ± 44.3 mm. In all cases, the Impella CP device was placed in left ventricle before PCI and removed a few minutes after the end of procedure, with a mean duration of mechanical circulatory support of 2.7 ± 0.8 hours. Only 1 (6.2%) patient died in hospital due to sepsis, whereas a clinically–evident bleeding occurred in 5 (31.3%) subjects (4 were access–site bleeding) and 4 (25%) patients underwent red blood cells transfusion; no acute limb ischaemia or aortic/left ventricle injury occurred. On a mean follow–up of 13 months from procedure date, any myocardial revascularization occurred in 2 (12.5%) patients, of whom 1 (6.2%) was a target–vessel revascularization. Four (25%) patients died but only 1 (6.2%) due to cardiac death: 2 subjects died as result of sepsis following pneumonia and 1 sepsis complicating gangrene. Conclusion Our study demonstrates the feasibility and efficacy of high–risk PCI protected by Impella CP, showing an acceptable long–term clinical outcome in a very high risk cohort of patients.