question: OBJECTIVE To test the hypothesis that intravenous thrombolysis (IVT) treatment prior to endovascular thrombectomy (EVT) is associated with better outcomes in patients with anterior circulation large artery occlusion (LAO) stroke, we examined a large real-world database, the SITS-International Stroke Thrombectomy Register (SITS-ISTR). METHODS We identified centers recording ≥10 consecutive patients in the SITS-ISTR, with at least 70% available modified Rankin Scale (mRS) scores at 3 months during 2014-19. We defined LAO as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Main outcomes were functional independence (mRS 0-2) and death at 3 months and symptomatic intracranial hemorrhage (SICH) per modified SITS-MOST. We performed propensity score matched (PSM) and multivariable logistic regression analyses. RESULTS Of 6350 patients from 42 centers, 3944 (62.1%) received IVT. IVT+EVT treated patients had less frequent atrial fibrillation, ongoing anticoagulation, previous stroke, heart failure and pre-stroke disability. PSM analysis showed that IVT+EVT patients had a higher rate of functional independence than EVT alone patients (46.4% vs. 40.3%, p<0.001) and a lower rate of death at 3 months (20.3% vs. 23.3%, p=0.035). SICH rates (3.5% vs. 3.0%, p= 0.42) were similar in both groups. Multivariate adjustment yielded results consistent with PSM. INTERPRETATION Pretreatment with IVT was associated with favorable outcomes in EVT-treated LAO stroke in the SITS Thrombectomy Registry. These findings, while indicative of international routine clinical practice, are limited by observational design, unmeasured confounding and possible residual confounding by indication. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that IVT prior to EVT increases the probability of functional independence at 3 months compared to EVT alone.