This clinical trial will evaluate whether on-site ischemic postconditioning (IPostC) improves outcomes in acute stroke patients receiving endovascular thrombectomy (EVT) and explore its mechanisms. The investigators aim to answer: (1) Is on-site IPostC effective compared to EVT alone? (2) What molecular markers and cellular pathways does on-site IPostC influence? Participants will be randomized to EVT alone or EVT+IPostC (4 cycles of 2-minute balloon occlusion/reperfusion). The investigators will assess infarct size, functional outcomes, biomarkers (e.g., multi-omics, ELISA, and clinical laboratory parameters), and safety (e.g., mortality, procedure-related complications).

This clinical trial is a single-center, prospective, blind endpoint, randomized -controlled trial. Randomization will be in a 1:1 ratio, Intervention Arm (EVT + on-site IPostC) or Control Arm (EVT alone) in up to a total of 60 patients (30 subjects in each arm). On-site IPostC will be initiated immediately upon successful recanalization (eTICI 2b-3) using low pressure balloon in situ of the location of thrombus, consisting of 4 cycles of 2-minute cycles of balloon inflation (occlusion) followed by 2 minutes of deflation (reperfusion).

Inclusion Criteria:

• The patient is ≥ 18 years of age.
• The patient must have symptoms consistent with AIS (i.e. face drooping, arm weakness, speech difficulty, etc.) , with symptoms severity of baseline NIHSS ≥ 6 and beginning less than 24 hours prior to presentation at hospital.
• Pre-stroke mRS ≤ 2.
• Baseline ASPECTS ≥ 6.
• Unilateral middle cerebral artery occlusion, and/or internal carotid artery occlusion.
• The patient is eligible for EVT.
• Successful recanalization achieved through EVT (eTICI 2b-3).
• The patient is willing to provide written informed consent to participate in this clinical trial.

Exclusion Criteria:

• The interventionalist deems the study device unable to reach the target site.
• Adverse events related to thrombectomy, such as contrast extravasation, vascular rupture/perforation, dissection, or embolization to a new territory, detected on post-thrombectomy angiography.
• Stent placement performed in the M1 segment of the middle cerebral artery or the terminal segment of the internal carotid artery during thrombectomy.
• Angioplasty of more than two cycles of balloon inflation/deflation.
• The patient is experiencing cardiogenic shock, systolic blood pressure [SBP] <100 mmHg, HR>100 bpm and arterial oxygen saturation (pulse oximetry) <92% without additional oxygen.
• The patient has known history of Congestive Heart Failure, hepatic failure, end-stage kidney disease or severe renal failure (clearance < 30ml/min/1.73m²).
• The patient is febrile (temperature > 37.5 °C) or has experienced an infection with fever in the last 5 days.
• The patient has a known hypersensitivity or contraindication to aspirin, heparin, Clopidogrel, tirofiban, or sensitivity to contrast media, which cannot be adequately pre-medicated.
• The patient has a known history of bleeding diathesis, coagulopathy, cryoglobulinemia, sickle cell anemia, or will refuse blood transfusions.
• The patient has a pre-AIS life expectancy of <1 year due to underlying medical conditions or pre-existing co-morbidities.
• The patient is currently enrolled in another investigational drug or device trial.
• The patient is apprehensive about or unwilling to undergo the required MRI imaging at follow-up, has a documented or suspected diagnosis of claustrophobia, or has Gadolinium allergy.
• The patient is a female who is known to be pregnant.
• Other conditions deemed unsuitable for inclusion by the investigator.

Plan Description: De-identified individual participant data (IPD) will not be made publicly available due to unresolved ethical considerations regarding data anonymization feasibility and institutional policies. A formal evaluation of data sharing options will be conducted post-study completion.

Access Criteria: Not applicable. IPD sharing is currently restricted. Future access may be negotiated via institutional data governance committees upon reasonable request.