Purpose: Mechanical thrombectomy (MT) is the standard of care for acute ischemic stroke (AIS) due to large vessel occlusion (LVO). The choice of a transradial approach (TRA) for anterior circulation LVOs is still debatable; the use of a specific tricoaxial system could help mitigate numerous issues related to transradial MT. Materials and Methods: From November 2022 to November 2023, 22 patients underwent TRA-MT for anterior circulation LVOs, both as first-line and rescue from transfemoral approach (TFA) failure, with the same triaxial setup consisting of a 7F introducer sheath, 7F guide catheter, and aspiration catheters ranging from 5.5F to 5F in relation to the occlusion site. Choice of thrombectomy technique was at operator discretion. Patients’ demographic data, clinical presentation, treatment details, complications, rate of crossover to TFA, successful revascularization (modified thrombolysis in cerebral infarction [mTICI] score ≥2b), and good clinical outcome at 3 months (modified Rankin scale [mRS] 0-2) were reported. Results: Of 20 patients selected, 10 (50%) had occlusion of M1 segment of middle cerebral artery (MCA), 6 (30%) of internal carotid artery (ICA) terminus, and 4 (20%) with M2 MCA occlusions; 12/20 (60%) were right-sided occlusions and 8/20 (40%) were left-sided. The mean National Institutes of Health Stroke Scale score was 9.25 at admission. Successful revascularization to mTICI 2b-3 was achieved in 18/20 patients (90%). Intracranial complications were reported in 2 (10%) patients. Rate of radial artery occlusion at 24 hours was 10,6%; no access-site haemorrhagic complications were reported. Symptomatic intracranial hemorrhage occurred in 2 (10%) patients. mRS score 0-2 at 3 months was 50%. Conclusion The high technical effectiveness and good safety profile of this specific tricoaxial setup for TRA-MT in AIS, even for large proximal LVOs, could constitute a viable alternative to TFA-MT in selected cases.