In patients at high risk for haemodynamic instability during percutaneous coronary intervention (PCI), practitioners are increasingly opting for prophylactic mechanical circulatory support, such as the Impella® heart pump (Abiomed, Danvers, MA, USA). Though Impellasupported high-risk PCI (HRPCI) ensures haemodynamic stability during the PCI procedure, access-related complication rates have varied significantly in published studies. Reported variability in complication rates relates to many factors, including anticoagulation practices, access and closure strategy, post-procedure care and variations in event definitions. This article aims to outline optimal strategies to minimize vascular and bleeding complications during Impella-supported HRPCI based on previously identified clinical, procedural and postprocedural risk factors. Practices to reduce complications include femoral skills training, standardized protocols to optimize access, closure, anticoagulation management and post-procedural care, as well as the application of techniques and technological advances. Protocols integrating these strategies to mitigate access-related bleeding and vascular complications for Impella-supported procedures can markedly limit vascular access risk as a barrier to appropriate large-bore mechanical circulatory support use in HRPCI.