ImportanceRecently, 6 randomized clinical trials—RESCUE-Japan-LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism—Japan Large Ischemic Core Trial), ANGEL-ASPECT (Trial of Endovascular Therapy for Acute Ischemic Stroke With Large Infarct), SELECT2 (Trial of Endovascular Thrombectomy for Large Ischemic Strokes), TESLA (Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke), TENSION (Endovascular Thrombectomy for Acute Ischemic Stroke With Established Large Infarct), and LASTE (Large Stroke Therapy Evaluation)—have concluded their investigations on the efficacy and safety of endovascular thrombectomy (EVT) for the treatment of patients with ischemic stroke, anterior-circulation large vessel occlusions, and large areas of ischemic changes defined as an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 5 or less. Overall, the results appeared to be positive, with 5 of the 6 trials meeting their primary efficacy end point, and 1 trial that was a near miss. However, questions remain regarding how these trial results should be interpreted and incorporated into routine clinical practice.ObservationsIn this narrative review and analysis of published trials, important nuances of the available clinical data were identified, and important areas of lingering uncertainty were highlighted, including the efficacy and safety of EVT for patients with a low ASPECTS score in late treatment windows and those with large core volumes. Also emphasized was the possibly important role of advanced neuroimaging modalities such as perfusion and magnetic resonance imaging when making EVT treatment decisions for select patients with low ASPECTS scores.Conclusions and RelevanceRecent trial data provide strong evidence that EVT is safe and effective for patients with anterior, large vessel–occlusion stroke and low ASPECTS scores who present within 6 hours from stroke onset. However, patient outcomes often remain poor despite EVT treatment. The efficacy and safety of EVT for patients with low ASPECTS scores who present beyond 6 hours of stroke onset remain uncertain, and the current trial data seem too scarce to justify forgoing advanced stroke imaging during this extended time window. Furthermore, the efficacy and safety of EVT for patients with large core volumes (100 mL or greater) or M2 occlusions (ie, occlusions of the second segment of the middle cerebral artery) remain uncertain. Future research to better identify patients likely to meaningfully respond to EVT is needed to further optimize the stroke triage process and health care resource utilization.