<b><i>Background:</i></b> The beneficial effects of endovascular therapy (EVT) in acute ischemic stroke have been demonstrated in recent clinical trials using new-generation thrombectomy devices. However, the comparative effectiveness and safety of preceding intravenous thrombolysis (IVT) in this population has rarely been evaluated. <b><i>Methods:</i></b> From a prospective multicenter stroke registry database in Korea, we identified patients with acute ischemic stroke who were treated with EVT within 8 h of onset and admitted to 14 participating centers during 2008-2013. The primary outcome was a modified Rankin Scale (mRS) score at 3 months. Major secondary outcomes were successful recanalization defined as a modified Treatment in Cerebral Ischemia score of 2b-3, functional independence (mRS score 0-2), mortality at 3 months, and symptomatic hemorrhagic transformation (SHT) during hospitalization. Multivariable logistic regression analyses using generalized linear mixed models were performed to estimate the adjusted odds ratios (ORs) of preceding IVT. <b><i>Results:</i></b> Of the 639 patients (male, 61%; age 69 ± 12; National Institutes of Health Stroke Scale score of 15 [11-19]) who met the eligibility criteria, 458 received preceding IVT. These patients showed lower mRS scores (adjusted common OR, 1.38 [95% CI 0.98-1.96]). Preceding IVT was associated with successful recanalization (1.96 [1.23-3.11]) and reduced 3-month mortality (0.58 [0.35-0.97]) but not with SHT (0.96 [0.48-1.93]). <b><i>Conclusion:</i></b> In patients treated with EVT within 8 of acute ischemic stroke onset, preceding IVT may enhance survival and successful recanalization without additional risk of SHT, and mitigate disability at 3 months.