With the increasing utilization of endovascular mechanical circulatory support devices, such as the Impella CP (Abiomed), there is a need for standardized guidelines for its safe removal. Development of the Perclose post-closure technique was facilitated by the introduction of a new Impella repositioning sheath in 2019, which enabled re-access to the sidearm and stylet, rewiring of the access artery, and Impella sheath removal. Our retrospective single-center study included all patients undergoing Perclose post-closure technique for vascular access closure after Impella removal between 2018 and 2024. Forty-six patients, with a mean age of 63.8 years, predominantly male (82.6%), were included in the analysis. Indications for Impella placement included complex percutaneous coronary intervention (34.8%) and cardiogenic shock (CS) (heart failure-CS: 32.6%, myocardial infarction-CS: 21.7%). Clinically relevant complications were encountered in less than 5% of cases. No instances of covered stent placement, fasciotomy, amputation, or access site infections were reported. Our study underscores the safety of the Perclose post-closure technique following Impella removal in a diverse cohort of patients, with an overall clinically significant complication rate of less than 5%. The Perclose post-closure technique is a reliable and well-tolerated method for vascular access closure in patients undergoing Impella support.