<p>Transcatheter aortic valve replacement (TAVR) has several alternative access routes when transfemoral access is unsuitable. This study compared perioperative and mid-term outcomes of transaxillary (TAx) TAVR with those of transapical (TA) and direct aortic (DA) approaches. Among 2,185 patients who underwent TAVR at our three centers between April 2015 and April 2024, 198 non-transfemoral cases were retrospectively analyzed. TAx-TAVR was classified as a non-thoracotomy approach, whereas TA/DA-TAVR were classified as thoracotomy approaches. Perioperative and mid-term outcomes were compared between the two groups. Of the 198 patients, 97 underwent the non-thoracotomy approach and 101 underwent thoracotomy (TA, <i>n</i> = 64; DA, <i>n</i> = 37). Most baseline characteristics were comparable, although dialysis-dependent patients were more common in the non-thoracotomy group. Operative time, transfusion requirement, and hospital stay were significantly greater in the thoracotomy group. Access-related complications included four events in the thoracotomy group (aortic injury or apical rupture) and five events in the non-thoracotomy group (aortic dissection or intimal injury). Postoperative ischemic stroke tended to occur more frequently in the non-thoracotomy group, though not significantly. One-year survival was significantly higher in the non-thoracotomy group, whereas mid-term mortality did not differ between groups. TAx-TAVR was associated with lower perioperative invasiveness and superior one-year survival compared with TA/DA-TAVR. However, the trend toward increased postoperative stroke underscores the importance of careful patient selection and thorough preoperative vascular assessment.</p> Graphical Abstract <p></p>