Background: Observational studies have demonstrated improved outcomes with the adjunctive use of balloon guide catheters (BGC) during endovascular thrombectomy (EVT) for anterior circulation acute ischaemic stroke (AIS). However, the lack of high-level evidence and global practice heterogeneity justifies a randomised controlled trial (RCT) to investigate the effect of transient proximal blood flow arrest on the procedural and clinical outcomes of patients with AIS following EVT. Hypothesis: Proximal blood flow arrest in the cervical internal carotid artery during EVT for proximal large vessel occlusion is superior to no flow arrest in achieving complete vessel recanalisation. Methods: ProFATE is an investigator-initiated, pragmatic, multicentre RCT with blinding of participants and outcome assessment. An estimated 124 participants with an anterior circulation AIS due to large vessel occlusion, an NIHSS of ⩾2, ASPECTS ⩾ 5 and eligible for EVT using a first-line combined technique (contact aspiration and stent retriever) or contact aspiration only will be randomised (1:1) to receive BGC balloon inflation or no inflation during EVT. Outcomes: The primary outcome is the proportion of patients achieving near-complete/complete vessel recanalisation (eTICI 2c-3) at the end of the EVT procedure. Secondary outcomes include the functional outcome (modified Rankin Scale at 90 days), new or distal vascular territory clot embolisation rate, near-complete/complete recanalisation after the first pass, symptomatic intracranial haemorrhage, procedure-related complications and death at 90 days. Discussion: This is the first RCT to investigate the effect of proximal blood flow arrest during EVT using a BGC on the procedural and clinical outcomes of patients with AIS due to large vessel occlusion.