Rationale: The Chemical Optimization of Cerebral Embolectomy (CHOICE) trial suggested that the administration of intra-arterial alteplase after successful endovascular thrombectomy (EVT) may improve neurological outcomes in patients with acute ischemic stroke due to large-vessel occlusion (AIS-LVO) in the anterior circulation. However, the use of adjunctive intra-arterial alteplase following successful EVT in acute posterior circulation stroke remains unexplored.Aims: This study aims to investigate the efficacy and safety of intra-arterial alteplase after successful EVT for AIS-LVO in the posterior circulation.Sample size: To detect an estimated 15% difference in the primary outcome between the two groups, a total of 376 patients will be enrolled. This sample size allows for 80% power and a 5% significance level, with an interim analysis planned after half of the sample (188 patients) has completed a 90-day follow-up.Methods and design: The Intra-arterial Alteplase Thrombolysis After Successful Thrombectomy for Acute Ischemic Stroke in the Posterior Circulation (IAT-TOP) trial is a multicenter, prospective, randomized clinical trial using an open-label treatment design with blinded endpoint assessment (PROBE) conducted in China. Patients with acute basilar artery occlusion will be randomly assigned in a 1:1 ratio to receive either intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) or standard care following successful thrombectomy (defined as expanded thrombolysis in cerebral infarction [eTICI] >= 2b50).Study outcomes: The primary outcome is the modified Rankin Scale (mRS) score of 0-2 at 90 days. Key secondary outcomes include changes in eTICI scores after intra-arterial thrombolysis (in the experimental group), mRS 0-3 at 90 days, ordinal shift analysis of mRS at 90 days, early neurological improvement at 48 h, and improvement in National Institutes of Health Stroke Scale (NIHSS) scores at 48 h and 7 days or discharge. Safety outcomes include symptomatic intracranial hemorrhage (sICH) rates at 48 h, 90-day mortality, non-intracranial hemorrhagic complications, and non-hemorrhagic serious adverse events.Discussion: The IAT-TOP trial will provide crucial evidence regarding the potential benefits of adjunctive intra-arterial alteplase in patients with AIS-LVO in the posterior circulation following successful thrombectomy.Trial registration: ClinicalTrials.gov NCT05897554