We sought to study the feasibility of axillary artery as alternative access for mechanical circulatory support (MCS) in cardiogenic shock and high-risk percutaneous coronary intervention (HR-PCI) patients with severe occlusive peripheral artery disease (PAD). In patients with severe PAD, the iliofemoral artery may be so diseased preventing deployment of MCS, precluding the use of lifesaving therapy. In such circumstances, the axillary artery may be a viable access site. Records of all patients presenting with cardiogenic shock or HR-PCI requiring MCS through axillary artery access at our institution from January 2016 to September 2018 were examined. Demographics, clinical, procedural, and outcomes data were collected on all patients. A total of 48 patients presented with cardiogenic shock (60%) or HR-PCI (40%) requiring MCS via axillary artery due to prohibitive PAD (mean age 66 ± 11 years). Admission diagnoses were non-ST segment elevation myocardial infarction (38%), unstable angina (23%), ST segment elevation myocardial infarction (19%), and cardiac arrest (21%). Time from axillary access to activation of Impella was 11.9 ± 4 minutes. Four patients required concomitant Impella RP for right ventricular support due to biventricular cardiogenic shock. Twenty-two patients died before Impella was explanted due to multiorgan failure, stroke, and infection. None of the patients who died had vascular complications related to axillary access. Axillary artery appears to be a viable alternative access for large bore devices in patients with prohibitive PAD. As experience of the field with this approach grows, it may be the default access for deployment of large bore sheaths in the future.