Introduction Thoracic endovascular aortic repair (TEVAR) carries a 3%–6.1% stroke risk, including risk of ‘silent’ cerebral infarction (SCI). Stent-grafts are manufactured in room air and retain air. Instructions for use recommend saline flushing to ‘de-air’ the system prior to insertion, but substantial amounts of air are released when deploying them, potentially leading to downstream neuronal injury and SCI. Carbon dioxide (CO2) is more dense and more soluble in blood than air, without risk of bubble formation, so could be used in addition to saline to de-air stents. This pilot trial aims to assess the feasibility of a full-scale randomised controlled trial (RCT) investigating the neuroprotective benefit against SCI with the use of CO2-flushed aortic stent-grafts.Methods and analysis This is a multicentre pilot RCT, which is taking place in vascular centres in the UK, USA and New Zealand. Patients identified for TEVAR will be enrolled after informed written consent. 120 participants will be randomised (1:1) to TEVAR-CO2 or TEVAR-saline, stratified according to TEVAR landing zone. Participants will undergo preoperative neurocognitive tests and quality of life assessments, which will be repeated at 6 weeks, or first outpatient appointment, and 6 months. Inpatient neurological testing will be performed within 48 hours of return to level 1 care for clinical stroke or delirium. Diffusion-weighted MRI will be undertaken within 72 hours postoperatively (1–7 days) and at 6 months to look for evidence and persistence of SCI. Feasibility will be assessed via measures of recruitment and retention, informing the design of a full-scale trial.Ethics and dissemination The study coordination centre has obtained approval from the London Fulham Research Ethics Committee (19/LO/0836) and Southern Health and Disability Ethics Committee (NZ) and UK’s Health Regulator Authority (HRA). The study has received ethical approval for recruitment in the UK (Fulham REC, 19/LO/0836), New Zealand (21/STH/192) and the USA (IRB 019-264, Ref 378630). Consent for entering into the study will be taken using standardised consent forms by the local study team, led by a local PI. The results of the trial will be submitted for publication in an open access journal.Trial registration number NCT03886675