Background: The use of Tenecteplase (TNK) in Extended Time Window (ETW) for Acute Ischemic Stroke (AIS) remains an ongoing debate. Methods: Systematic review of 3 Randomized controlled trials (RCTs)- TIMELESS, TRACE 3, CHABLIS-T II was conducted. Results: 1198 patients were enrolled: 603 received TNK, while 595 were controls. All 3 trials included patients with Internal Carotid and/ or Proximal Middle Cerebral Artery Occlusions; however, in TRACE 3, patients did not have access to endovascular thrombectomy. TIMELESS and CHABLIS-T II showed better recanalization in the TNK group but the median Modified Rankin Score was 3 at 90 days in both groups, demonstrating no benefit in clinical outcomes. Symptomatic Intracranial hemorrhage (sICH) was similar in the two groups. In TRACE 3, there was an improvement in functional outcomes at 90 days in the TNK group (33.0% vs. 24.2%), but the incidence of sICH was also higher (3.0% and 0.8%, respectively). Conclusions: Better recanalization rates are seen with TNK in ETW, but may not be associated with improved functional outcomes at 90 days compared to medical management. Incidence of sICH also remains largely favorable, except in TRACE 3, which showed a higher incidence in the TNK group. There remains a need for more RCTs in this population.