Background: Albumin is a multifunctional plasma protein that is mainly synthesized in the liver and may play a neuroprotective role in treating acute ischemic stroke (AIS). The efficacy of albumin in patients with AIS receiving reperfusion therapy remains unknown. Methods: ARISE is a multicenter, randomized, double-blind, placebo-controlled, phase 2 study. We will recruit 134 patients aged 18-80 years with AIS due to large-vessel occlusion in the anterior circulation, within 24 h of symptom onset, with an Alberta Stroke Program Early CT Score of 3-10 points and an infarct core volume of <= 100 mL at baseline. Eligible patients will be randomly assigned, on a 1:1 ratio, to undergo endovascular therapy (EVT) and receive albumin therapy (0.5 g/kg; intravenous injection) once daily for 4 days or to undergo EVT and receive placebo therapy once daily for 4 days. The primary efficacy outcome is the change in infarct volume from baseline to day 5. Conclusion: The ARISE trial will provide valuable evidence on the efficacy and safety of albumin in patients with AIS receiving EVT. Clinical trial registration: www.clinicaltrials.gov, NCT06538844.