BackgroundsIncreased blood pressure (BP) for patients who had an acute ischaemic stroke is associated with poor functional outcome, however the optimal timing of antihypertensive therapy is unknown.AimsWe aim to compare early antihypertensive treatment to delayed antihypertensive treatment for reducing the risk of composite major disability and mortality at 3 months in acute ischaemic stroke.DesignThe China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) trial is a multicentre, randomised, open-label, blinded-endpoints trial that will be conducted in 100 hospitals in China. The primary outcome is the composite of death and major disability (modified Rankin Scale score ≥3) at 3 months of randomisation. Antihypertensive treatment will be received immediately after randomisation in the early treatment group, aimed at average systolic BP by 10%–20% reduction within the first 24 hours, and achieving an average BP level of <140/90 mm Hg within 5 days. Patients in the delayed treatment group will discontinue any antihypertension medications for the first 7 days of randomisation, and will receive antihypertensive therapy achieving a BP goal of <140/90 mm Hg after 7 days.ConclusionThe CATIS-2 trial will be testing the hypotheses that early BP lowering leads to improved functional outcome without any other harms, and developing clinical guidelines of the BP management for patients who had an acute ischaemic stroke.Trial registration numberNCT03479554.