ObjectiveTo evaluate the safety and efficacy of intra-arterial thrombolysis (IAT) as an adjunct to endovascular thrombectomy (EVT) in ischemic stroke, we performed a systematic review and meta-analysis of the literature.MethodsSearches were performed using MEDLINE, Embase, and Cochrane databases for studies that compared EVT with EVT with adjunctive IAT (EVT + IAT). Safety outcomes included symptomatic intracerebral hemorrhage and mortality at 3 months. Efficacy outcomes included successful reperfusion (Thrombolysis in Cerebral Infarction score of 2b–3) and functional independence, defined as a modified Rankin Scale score of 0–2 at 3 months.ResultsFive studies were identified that compared combined EVT + IAT (IA alteplase or urokinase) with EVT only and were included in the random-effects meta-analysis. There were 1693 EVT patients, including 269 patients treated with combined EVT + IAT and 1,424 patients receiving EVT only. Pooled analysis did not demonstrate any differences between EVT + IAT and EVT only in rates of symptomatic intracerebral hemorrhage (odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.20–1.85;p= 0.78), mortality (OR: 0.77, 95% CI: 0.54–1.10;p= 0.15), or successful reperfusion (OR: 1.05, 95% CI: 0.52–2.15;p= 0.89). There was a higher rate of functional independence in patients treated with EVT + IAT, although this was not statistically significant (OR: 1.34, 95% CI: 1.00–1.80;p= 0.053).ConclusionAdjunctive IAT appears to be safe. In specific situations, neurointerventionists may be justified in administering small doses of intra-arterial alteplase or urokinase as rescue therapy during EVT.