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Objective To investigate the efficacy and safety of intravenous thrombolysis with low-dose and standard-dose recombinant tissue plasminogen activator (rt-PA) in the elderly patients (aged over 80 years) with acute ischemic stroke (AIS). Methods A total of 201 elderly patients with AIS treated at Tianjin Fourth Central Hospital from February 2019 to February 2023 were prospectively included and randomly assigned to the rt-PA low-dose group (n = 93, 0.6 mg/kg) and rt-PA standard-dose group (n = 108, 0.9 mg/kg). The incidence of intra-cranial hemorrhage, symptomatic intracranial hemorrhage, fatal intracranial hemorrhage, neurologic deterioration within 7 days and mortality within 90 days were observed to evaluate the safety. The neurologic improvement rate and good prognosis rate at 90 days were used to evaluate the effectiveness. A stratified analysis of 90-day outcomes was performed based on stroke severity and age. Results The incidence of intracranial hemorrhage, symptomatic intracranial hemorrhage and fatal intracranial hemorrhage within 7 days in rt-PA low-dose group was lower than that in rt-PA standard-dose group (P < 0.05). There were no statistically significant differences between the two groups concerning the residual safety index and the effectiveness index. The 90-day good prognosis rate of moderate stroke sub-group and of 5 90 years of age sub-group in rt-PA low-dose group were both higher than that of rt-PA standard-dose group (P < 0.05 ). Conclusions For AIS patients with moderate stroke and aged over 90 years, intravenous thrombolytic therapy with rt-PA 0.6 mg/kg is recommended. [ABSTRACT FROM AUTHOR]