Introduction: Recently, percutaneous ventricular assist device (p-LVAD) has been widely applicable for cardiogenic shock. Clinically significant aortic insufficiency (AI) is contraindication for p-LVAD, nevertheless p-LVAD itself can cause de novo AI (dAI) during the support. However the detail of dAI during p-LVAD support was not fully investigated. The aim of this study was to evaluate the clinical impact of AI during p-LVAD support and also investigate the mechanism and risk factor of dAI. Methods: Seventy-seven consecutive patients who underwent p-LVAD support (average age 66.7 years, Impella CP/2.5 in 65 and 5.5/5.0 in 12 cases) from 2018 to 2022 were retrospectively evaluated. The average support periods was 8.0±6.9 days. dAI was defined as development of AI ≥ moderate during p-LVAD support. Aortic valve pathology was examined using autopsy specimens in eight patients. Results: Three patients had AI ≥ moderate before p-LVAD support and underwent surgical intervention (AVR in 2 and AV repair in 1) during p-LVAD support. dAI was observed in 8 patients (10.3%, moderate in 7 and severe in 1). Moderate dAI in four of these patients improved after cardiac recovery and weaning of p-LVAD support. However, in 3 other patients with dAI ≥ moderate developed hemodynamic instability and deceased due to heart failure. In only a patient, moderate dAI remained after p-LVAD weaning with stable hemodynamics. Progression of AI after p-LVAD removal was not observed in all patients. In-hospital mortality was higher in the patient with dAI (75.0 vs. 47.8%, p=0.14). Pathological evaluation revealed hemorrhagic change at LV side of aortic valve with hemosiderin-laden macrophages in 3 autopsy specimens, which suggested contact of p-LVAD catheter. The univariate analysis identified mild AI before p-LVAD support as independent risk factor for dAI (Odd ratio 5.5, 95%CI 0.074-0.45, p<0.001). Conclusions: Our study demonstrated that de novo AI frequently occurred during p-LVAD support and had a negative impact on hemodynamics and prognosis. Interference with aortic valve by the p-LVAD catheter may cause and exacerbate AI, even in the cases with pre-existing mild AI. Surgical intervention is essential to improve hemodynamics for severe and permanent AI during p-LVAD support.