Background and Aims Currently, conventional total arch replacement remains the main treatment for lesions involving the aortic arch. Conventional total arch replacement requires completion under the open chest and cardiopulmonary bypass, with a surgical duration of over 10 hours, earning it the title of a "bloody, night-long, life-or-death" surgery. Due to the unique anatomical structure of the aortic arch, it has long been considered a "forbidden zone" for endovascular treatment. Although intra-aortic techniques for the aortic arch are advancing rapidly, the bottleneck issue still needs to be solved, making it difficult to be widely applied in clinical practice. Here, the authors report the results of the first-in-man (FIM) study of a new femoral endovascular access supra-arch branched stent graft for treating aortic arch lesions to evaluate its application effectiveness and safety preliminarily.Methods The clinical results of 3 patients with aortic arch lesions treated using the femoral endovascular access supra-arch branched stent graft at the First Affiliated Hospital of Air Force Medical University from October 2023 to December 2023 were analyzed. Patient baseline information, lesion characteristics, intraoperative parameters, postoperative aortic arch repair, and related complications were collected.Results All three patients were male, aged between 50 and 74. All surgeries were successful without short-term postoperative complications or deaths. The three patients included one case of aortic arch coarctation aneurysm and two cases of aortic arch aneurysm with ulceration; two of them presented with chest pain, and one was incidentally found during physical examination. All three patients had concomitant hypertension, and one had diabetes. The lesions in two patients were located in zones 1-3, involving the left common carotid artery, and in one patient, the lesion was located in zones 0-3, involving the innominate artery and the left common carotid artery. The average operative time was 125 min. One patient was admitted to the intensive care unit (ICU) with catheter indwelling, while the remaining two had their catheters removed in the operating room. There was no cerebral ischemia process, and no cardiovascular or cerebrovascular complications occurred during the operation. The stents were all introduced via the femoral artery route, and the implantation was smooth. Intraoperative digital subtraction angiography showed excellent position and shape of the stent graft with good patency, complete isolation of the lesion area, and no adverse events such as endoleak or branch artery stenosis. The average length of ICU stay was 31 h. Postoperative reexamination of aortic vascular imaging showed good positions of the main and branch stents, good isolation of the lesions, and no endoleak or branch vessel stenosis or occlusion. There were no postoperative cardiovascular and cerebrovascular complications.Conclusion Applying this new femoral endovascular access supra-arch branched stent graft to treat aortic arch lesions results in no cerebral ischemia during the operation. Moreover, the delivery system is accessed via the femoral artery route, making the procedure more straightforward and reducing trauma further. The surgery proceeds uneventfully, with good outcomes, and the short-term postoperative efficacy is satisfactory, indicating promising clinical application prospects.