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Background: Endovascular therapy (EVT) has been proven beneficial for treating acute ischemic strokes (AIS) with large vessel occlusion (LVO). Recent trials of DAWN and DEFUSE-3 have extended the treatment window to 6–24 h, sparking investigations into EVT outcomes for patients not eligible for DAWN/DEFUSE-3 criteria. Purpose: To assess the outcomes of endovascular therapy (EVT) for late-window anterior circulation large vessel occlusion (LVO) in acute ischemic stroke patients, comparing DAWN/DEFUSE-3 eligible (DD) and ineligible (NDND) groups. Methods: This systematic review and meta-analysis examined EVT outcomes for patients with late-window anterior circulation LVO beyond 6 h. We categorized patients as DAWN/DEFUSE-3 eligible (DD) and ineligible (NDND). Our search covered PubMed, Embase, Web of Science, and Scopus. A total of 464 records were initially identified. After duplicate removal, 298 studies were screened. Nine studies were included and analyzed. Our analysis focused on study characteristics, baseline comparisons, risk of bias, and outcomes. Results: Baseline characteristics showed comparable age, gender, most comorbidities, NIHSS score, and ASPECTS between DAWN/DEFUSE-3 eligible (DD) and ineligible (NDND) patients. NDND patients' history showed a higher rate of atrial fibrillation and larger infarct volumes on baseline imaging. Successful reperfusion rates (TICI 2b-3) were similar between DD and NDND with 354 out of 469 in the DD group and 364 out of 459 in the NDND group (OR = 0.86; 95% CI 0.40, 1.84; p = 0.689), though with significant heterogeneity (I2 = 73%; P = 0.002). The proportion of patients with distal occlusions was significantly higher in the NDND group as compared to the DD group (137 (39.4%) of 347 patients versus 47 (11%) of 428 patients, respectively), with significant heterogeneity across studies (I2 = 85%, p = 0.023). Functional independence at 90 days (mRS 0–2) showed no significant difference between groups with 259 out of 802 in the DD group and 197 out of 668 in the NDND group (OR = 1.12; 95% CI 0.77, 1.63; p = 0.552) but also exhibited notable heterogeneity (I2 = 46%, p = 0.063). Symptomatic intracranial hemorrhage (sICH) rates were lower in DD with 14 out of 309 in the DD group and 47 out of 400 in NDND group (OR = 0.49; 95% CI 0.25, 0.93; p = 0.029) as compared to the NDND patients, showing no heterogeneity (I2 = 0%, p = 0.552). 90-day mortality was lower in DD with 43 out of 304 in the DD group and 107 out of 399 in the NDND group (OR = 0.55; 95% CI 0.37, 0.82; p = 0.004) as compared to NDND patients, with no significant heterogeneity (I2 = 0%, p = 0.536). Conclusion: This meta-analysis demonstrates equivalent rates of functional independence between DD and NDND patients. However, the high proportion of distal occlusions and higher rates of sICH and mortality in NDND patients suggest caution in offering mechanical thrombectomy to DAWN/DEFUSE-3 ineligible patients. A more flexible approach to EVT eligibility criteria could benefit select patients in real-world practice. Nonetheless, further research is needed to identify which patients would benefit from expanded EVT eligibility criteria. [ABSTRACT FROM AUTHOR]