DEFUSE-3 is a randomized clinical trial comparing endovascular therapy and standard medical management with medical management alone in anterior circulation large vessel occlusion (LVO) acute ischemic stroke (AIS) patients presenting within 6 to 16 hours from last well-known time with salvageable ischemic brain tissue. The penumbral regions determined on perfusion scans was calculated with the use of automated RAPID software and patients were eligible if they had initial infarct volume of <70mL, mismatch ratio >= 1.8, and an absolute penumbra volume of >=15mL. Following successful results of DAWN trial, an early interim analysis was performed and the DEFUSE-3 trial was terminated early for efficacy. A total of 182 patients were randomized to endovascular group (n=92) and medical group (n=90). The primary outcome of favorable shift on modified rankin scale (mRS) at 90 days had an odds ratio of 2.77 favoring endovascular therapy with number needed to treat to reduce disability of 2. In endovascular therapy group, significantly higher percentage of patients achieved functional independence (mRS 0-2) 45% vs 17%, and mortality rates were significantly lower 14% vs 26%. There was non-significant higher symptomatic intracerebral hemorrhage in the endovascular group 7% vs 4% (p=0.75). With publication of DEFUSE and DAWN trials there is now class I: level of evidence A to perform mechanical thrombectomy between 6-24 hours for anterior circulation LVO AIS patients who meet eligibility criteria of these trials.