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Rationale: Acute kidney injury (AKI) is common during high-risk percutaneous coronary intervention (PCI), particularly in those with severely reduced left ventricular ejection fraction. The impact of partial hemodynamic support with a microaxial percutaneous left ventricular assist device (pLVAD) on renal function after high-risk PCI remains unknown. Objective: We tested the hypothesis that partial hemodynamic support with the Impella 2.5 microaxial pLVAD during high-risk PCI protected against AKI. Methods and Results: In this retrospective, single-center study, we analyzed data from 230 patients (115 consecutive pLVAD-supported and 115 unsupported matched-controls) undergoing high-risk PCI with ejection fraction ≤35%. The primary outcome was incidence of in-hospital AKI according to AKI network criteria. Logistic regression analysis determined the predictors of AKI. Overall, 5.2% (6) of pLVAD-supported patients versus 27.8% (32) of unsupported control patients developed AKI ( P P P P =0.04 and adjusted odds ratio, 0.16; 95% confidence intervals, 0.12–0.28; P Conclusions: Impella 2.5 (pLVAD) support protected against AKI during high-risk PCI. This renal protective effect persisted despite the presence of underlying CKD and decreasing ejection fraction.