BACKGROUND AND PURPOSE: In a recent pooled analysis of randomized clinical trials (RCTs), intravenous tissue plasminogen activator (TPA) improves the outcome in patients aged > or =80 years. However, it is uncertain whether the findings are applicable to clinical practice in Asian populations. METHODS: From a multicenter stroke registry database of Korea, we identified patients with acute ischemic stroke who were aged > or = 80 years. Using multivariable analysis and propensity score (PS)-matched analyses, we assessed the effectiveness and safety of intravenous TPA within 4.5 hours. RESULTS: Among 2,334 patients who met the eligible criteria, 236 were treated with intravenous TPA (mean age, 83+/-5; median NIHSS, 13 [IQR, 8-17]). At discharge, the TPA group compared to the no-TPA group had a favorable shift on the modified Rankin Scale (mRS) score (multivariable analysis, OR [95% CI], 1.51 [1.17-1.96], P=0.002; PS-matched analysis, 1.54 [1.17-2.04], P=0.002) and was more likely to achieve mRS 0-1 outcome (multivariable analysis, 2.00 [1.32-3.03], P=0.001; PS-matched analysis, 1.59 [1.04-2.42], P=0.032). TPA treatment was associated with an increased risk of symptomatic intracranial hemorrhage (multivariable analysis, 5.45 [2.80-10.59], P<0.001; PS-matched analysis, 4.52 [2.24-9.13], P<0.001), but did not increase the in-hospital mortality (multivariable analysis, 0.86 [0.50-1.48], P=0.58; PS-matched analysis, 0.88 [0.52-1.47], P=0.61). CONCLUSIONS: In the setting of clinical practice, intravenous TPA within 4.5 hours improved the functional outcome despite an increased risk of symptomatic intracranial hemorrhage in very elderly Korean patients. The findings, consistent with those from pooled analysis of RCTs, strongly support the use of TPA for this population.