OBJECTIVE: The aim of this study was to identify factors associated with difficulty in establishing vascular access during the transradial approach for neurointerventional therapy. METHODS: We retrospectively analyzed consecutive patients who successfully underwent transradial approach neurointerventional therapy at Fudan Zhongshan Xiamen Hospital (July 2021-July 2024). Patients were categorized as "difficult" or "easy" according to whether vascular access establishment required >15 min. Collected variables included difficulty in radial artery puncture/sheath insertion, feasibility of routinely forming a Simmons-2 catheter, aortic arch type (II-III), tortuosity of the brachiocephalic trunk, brachiocephalic trunk-target common carotid artery angle (<30°), and tortuosity of the C2-C4 internal carotid artery. Multivariate logistic regression was performed to identify independent factors. RESULTS: Among 277 patients, 199 were in the easy group and 78 were in the difficult group. Compared with the easy group, the difficult group more frequently had difficult radial puncture/sheath insertion, brachiocephalic trunk tortuosity, a sharp brachiocephalic trunk-target common carotid artery angle (<30°), C2-C4 internal carotid artery tortuosity, and failure to routinely form a Simmons-2 catheter (all p<0.05). Hypertension, diabetes, hyperlipidemia, and type III aortic arch were not significantly different between groups (all p>0.05). On multivariate analysis, difficult radial puncture/sheath insertion, inability to routinely form a Simmons-2 catheter, brachiocephalic trunk tortuosity, a brachiocephalic trunk-target common carotid artery angle <30°, and C2-C4 internal carotid artery tortuosity were independent factors associated with access difficulty (all p<0.001). CONCLUSION: Both access-site difficulty and unfavorable supra-aortic/internal carotid artery anatomy were independently associated with prolonged vascular access establishment during transradial approach neurointerventional therapy.