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Background: Transcarotid artery revascularization (TCAR) is an interventional therapy for symptomatic internal carotid artery disease. Currently, the utilization of TCAR is contentious due to limited evidence. In this study, we evaluate the safety and efficacy of TCAR in patients with symptomatic internal carotid artery disease compared with carotid endarterectomy (CEA) and carotid artery stenting (CAS)., Methods: A systematic review was conducted, spanning from January 2000 to February 2023, encompassing studies that used TCAR for the treatment of symptomatic internal carotid artery disease. The primary outcomes included a 30-day stroke or transient ischemic attack, myocardial infarction, and mortality. Secondary outcomes comprised cranial nerve injury and major bleeding. Pooled odds ratios (ORs) for each outcome were calculated to compare TCAR with CEA and CAS. Furthermore, subgroup analyses were performed based on age and degree of stenosis. In addition, a sensitivity analysis was conducted by excluding the vascular quality initiative registry population., Results: A total of 7 studies involving 24 246 patients were analyzed. Within this patient cohort, 4771 individuals underwent TCAR, 12 350 underwent CEA, and 7125 patients underwent CAS. Compared with CAS, TCAR was associated with a similar rate of stroke or transient ischemic attack (OR, 0.77 [95% CI, 0.33-1.82]) and myocardial infarction (OR, 1.29 [95% CI, 0.83-2.01]) but lower mortality (OR, 0.42 [95% CI, 0.22-0.81]). Compared with CEA, TCAR was associated with a higher rate of stroke or transient ischemic attack (OR, 1.26 [95% CI, 1.03-1.54]) but similar rates of myocardial infarction (OR, 0.9 [95% CI, 0.64-1.38]) and mortality (OR, 1.35 [95% CI, 0.87-2.10])., Conclusions: Although CEA has traditionally been considered superior to stenting for symptomatic carotid stenosis, TCAR may have some advantages over CAS. Prospective randomized trials comparing the 3 modalities are needed., Competing Interests: Disclosures Dr Matouk is a consultant for Silk Road Medical, MicroVention, Inc, and Penumbra, Inc. Dr Derdeyn is involved in data and safety monitoring at Penumbra (MIND and THUNDER trials), NoNO (ESCAPE NEXT and FRONTIER), and Silk Road (NITE trial); has stock options in Euphrates Vascular; and is a professor and a chair at The University of Iowa. Dr Levy is a shareholder and has ownership interest in NeXtGen Biologics, Claret Medical, Inc, Imperative Care, Inc, Rebound Therapeutics, StimMed, and Three Rivers Medical; is a consultant at Clarion, GLG Consulting, Guidepoint Global, Misionix, Mosaic, and StimMed and at Medtronic Vascular, Inc, Microvetion, and Penumbra, Inc; and has stock options in Rapid Medical Ltd. Dr de Havenon has stock options at Certus and TitinKM, received grant/contract from the National Institutes of Health, and is a consultant at Novo Nordisk. Dr Leira received a grant/contract from the American Stroke Association and is a professor of neurology, neurosurgery, and epidemiology at the University of Iowa. Dr Henninger received a grant/contract from the National Institutes of Health and the US Department of Defense and is an associate professor at the University of Massachusetts Medical School. Dr Chaturvedi received a grant/contract from Mayo Clinic. The other authors report no conflicts.