Carotid endarterectomy (CEA), carotid artery stenting (CAS) and best medical therapy (BMT) are the major treatments used for significant asymptomatic carotid artery stenosis (ACAS, ≥50%). However, the widespread use of lipid-lowering drugs in this century has improved BMT outcomes. This study aims to compare the treatment efficacy of current BMT, CEA+BMT and CAS+BMT in patients with significant ACAS. This protocol was designed based on the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Publication time for studies will be set from 1 January 2000 to 1 June 2020. We will search three databases: PubMed, EMBASE and The Cochrane Library. Suitable randomised controlled studies will be screened. The primary outcomes will include short-term and long-term mortality, stroke and myocardial infarction. OR and HR for dichotomous data and time-to-event data with 95% CIs will be calculated. Treatment effects among different therapies will be ranked according to the surface under the cumulative ranking curve and mean rank. A comprehensive evaluation of the risk of bias, heterogeneity and transitivity will be performed before data synthesis. Consistency and evidence quality will also be assessed. There will be no need for ethics approval as this systematic review is a summary and analysis of existing literature. Final results may be presented in international conferences or a peer-reviewed journal. CRD42019138942. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.