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Background and purpose: Patients estimated to have a large irreversibly injured ischemic core are sometimes excluded from reperfusion therapies. We examined the association between estimated core volume and thrombectomy outcomes.Methods: Patient-level CT perfusion (CTP) and clinical data were pooled from trials comparing endovascular thrombectomy with standard care in anterior circulation ischemic stroke: MR CLEAN, EXTEND IA, ESCAPE, SWIFT PRIME, REVASCAT and PISTE. Ischemic core volume was estimated using relative cerebral blood flow <30% of normal brain (RAPID automated software, IschemaView). The primary outcome was the 90 day modified Rankin scale (mRS), adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modeling with a random effect for trial incorporated in all models.Results: Of 1352 patients, pre-treatment CTP was assessable in 539 after exclusion of 27 patients (12 severe motion, 2 no lesion within coverage, 2 contrast bolus failure, 11 data corruption during transfer from site). There were 264 allocated to endovascular thrombectomy and 275 to control. Baseline characteristics were similar between endovascular and control patients with CTP, median core 9.6 mL (IQR 2.4-26 mL) and with the overall trial demographics. Larger estimated core volume was associated with lower probability of independent outcome (mRS 0-2) in endovascular (OR 0.87 95%CI 0.80-0.95) and control patients (OR 0.85 95%CI 0.77-0.93, core*treatment interaction p=0.62) and increased disability: utility scores derived from mRS reduced by 2% (95%CI 1-4%) per 10mL increase in core volume for both endovascular and control patients (core*treatment interaction p=0.79). However, patients with >70mL core (median 100 mL, IQR 82-144mL) still benefitted from thrombectomy: ordinal mRS cOR 7.0 (2.6 -18.9) and the number needed to treat (NNT) remained stable across the spectrum of core volumes (point estimate NNT<10 for mRS 0-2 and NNT<3 for improvement in at least 1 mRS level).Conclusions: Increasing estimated core volume was independently associated with worse outcome but endovascular thrombectomy remained effective versus standard care even in patients with large core who otherwise met eligibility for these trials.