Abstract Background Patients undergoing carotid endarterectomy (CEA) have a high restenosis rate, which increases the risk of stroke, and there is still a lack of effective treatment for restenosis. The cause of stenosis is related to local inflammatory reactions. Some basic studies have shown that the inflammatory response causing arterial stenosis is closely related to the nerve axons distributed in its outer membrane, and that removal of the nerve is effective in reducing the inflammatory response to prevent arterial stenosis. Therefore, we propose to design a randomized controlled trial to study whether disconnecting the carotid sinus nerve during a CEA operation can reduce carotid arterial restenosis. Method/design This study is a randomized, double-blind, single-center study. We will recruit 276 patients, who will be randomly divided into the experimental group and the control group. Based on the standard CEA operation, the operator will search for the carotid sinus nerve on the surface of the internal carotid artery and will entirely transect it in the experimental group. Both groups will be guided with the same postoperative treatment and will be followed up every 3 months for 3 years after the operation. The main indices observed will be the carotid restenosis rate, incidence and nature of carotid plaque, and carotid blood flow velocity. Other indices will be arrhythmia, blood pressure variability, and biomarkers of atherosclerosis, such as blood lipids, hypersensitive C-reactive protein (hs-CRP), homocysteine, and total bilirubin. Discussion It is expected that carotid sinus nerve transection will significantly reduce the occurrence of restenosis after CEA, decrease the incidence of ischemic stroke, and realize the effective primary prevention of stroke. Trial registration ChiCTR2300073652. Registered on July 18, 2023.