Percutaneous transaxillary approach (PTAX) through the first segment of the axillary artery is not widely recognized as a safe method. Furthermore, PTAX has never been directly compared between Impella-supported percutaneous coronary interventions (Impella-PCI) and transcatheter aortic valve replacement (TAVR). This study evaluated the feasibility and safety of PTAX through the first axillary segment in Impella-PCI versus TAVR. In cases where standard imaging guidance was insufficient, a technique involving puncturing the axillary artery “on-the-balloon” was employed. The endpoints were bleeding and vascular complications, as defined by BARC and VARC-3 criteria. PTAX was successfully performed in all 46 attempted cases: 23 for Impella-PCI and 23 for TAVR. Strict adherence to BARC and VARC-3 criteria led to the frequent identification of major bleeding (57%) and a moderately frequent diagnosis of vascular complications (17%). These incidences were primarily based on post-procedural hemoglobin reduction (> 3 g/dl) but not overt bleeding. The Impella group exhibited a higher rate of BARC 3b bleeding due to a greater hemoglobin decline resulting from the prolonged implant duration and PCI itself. Left axillary access was linked to smaller blood loss. Bleeding and vascular complications, as per BARC and VARC-3 definitions, did not affect short-term prognosis, with only 3 Impella patients succumbing to heart failure unrelated to the procedures during one-month follow-up period.