BACKGROUND: As a noninvasive, low-cost, nonpharmacological procedure with excellent properties of safety, remote ischemic conditioning (RIC) has been demonstrated to prevent recurrence of stroke among patients with ischemic stroke of large artery atherosclerosis origin. We hypothesized that the benefit is attributed to the improvement of collaterals by chronic RIC in this population, and we aimed to explore the influence of chronic RIC on collateral status evaluated by digital subtraction angiography in this population. METHODS: The RICAS (Remote Ischemic Preconditioning on Collaterals of Atherosclerosis Stroke) study is a prospective, randomized, blind end point, multicenter study. Eligible patients with ischemic stroke of anterior circulation caused by large artery atherosclerosis, poor collateral compensation, and more than 1 month of symptom onset, are randomly assigned into experimental and control groups with a ratio of 1:1. The patients in the experiment group will receive treatment with RIC (bilateral upper limbs, for a total procedure time of 50 minutes, twice daily) for 1 year as an adjunct to guideline-based treatment, while patients in the control group only receive guideline-based treatment. A maximum of 300 patients (150 participants per group) are required to test the superiority hypothesis with 80% power (using a 2-sided CONCLUSIONS: This study may provide the direct evidence for the potential effect of chronic RIC treatment on the improvement of collateral status. REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT06170944.