Intra-arterial thrombolytic therapy (IAT) may be a treatment option for patients with ischemic stroke. We analyzed the safety and efficacy of IAT on the basis of published data. We searched computerized databases for studies using IAT in >/=10 patients with ischemic stroke. Some studies had control patients for comparison. Data were collected on age, stroke territory, time to treatment, medication, site of arterial occlusion and recanalization on angiogram, outcomes, and symptomatic intracranial hemorrhage (SICH). The analysis included 27 studies with 852 patients who received IAT and 100 control subjects. There were more favorable outcomes in the IAT than in the control group (41.5% versus 23%, P=0.002), with a lower mortality rate for IAT (IAT, 27.2%; control group, 40%, P=0.004). The IAT group had an odds ratio of 2.4 (95% CI, 1.45 to 3.85) for favorable outcome. SICH was more frequent in the IAT group compared with the control group (9.5% versus 3%, P=0.046). The subgroup of patients receiving a combination of intravenous thrombolytic therapy and IAT had more favorable outcomes than the IAT alone subgroup, but this trend did not reach statistical significance (53.6% versus 41.5%, P=0.1). Among the patients treated with IAT, those who had supratentorial strokes were more likely to have favorable outcomes than those with infratentorial strokes (42.2% versus 25.6%; P=0.001; odds ratio, 2.0; 95% CI, 1.33 to 3.0). IAT for ischemic stroke appears efficacious but carries an increased risk of SICH. Further prospective studies are needed to prove the safety and efficacy of IAT in stroke.