New evidence supports administering intravenous tenecteplase prior to endovascular thrombectomy in patients with acute ischemic stroke caused by large-vessel occlusion. Study participants presented within 4.5 hours of stroke onset, with 272 subsequently randomized to endovascular thrombectomy alone and 278 randomly assigned to receive I.V. tenecteplase first. At 90-day follow-up, 52.9% of patients who underwent tenecteplase and then thrombectomy achieved the primary endpoint of functional independence compared with 44.1% of patients in the thrombectomy-only treatment arm. Among safety outcomes, symptomatic intracranial hemorrhage occurred within 48 hours in 8.5% of tenecteplase recipients vs. 6.7% of patients undergoing thrombectomy only. The 90-day mortality rate was 22.3% and 19.9%, respectively.