Introduction Intracranial atherosclerosis is the main cause of stroke globally, with acute large vessel occlusive (LVO) stroke being a predominant contributor to stroke-related mortality. In recent years, aspiration thrombectomy (AT) has emerged as a novel therapeutic method for treating acute LVO stroke. The purpose of this study aims to investigate the safety and efficacy of AT alone or combined with stent retriever thrombectomy (SRT) in the treatment of acute LVO stroke Methods and analysis This is a multicentre and observational real-world study involving patients diagnosed with acute LVO stroke. Participants will be treated with AT alone or combined with SRT. According to the actual annual number of embolectomy in the sub-centre and the research years, the sample size of this study is estimated to be 400 patients, of which 300 patients of anterior circulation lesions and 100 patients of posterior circulation lesions are planned to be recruited, being considered that the incidence of posterior circulation is about 20-25%. Clinical data, including baseline characteristics, intraoperative details, postoperative outcomes and follow-up results, will be systematically collected using an Electronic Data Capture system over a follow-up period of 3 months. The primary efficacy endpoint is the rate of excellent functional outcome (modified Rankin Scale score range 0-3) after 90 days, and the successful recanalisation confirmed by digital subtraction angiography. The primary safety outcome is symptomatic intracranial haemorrhage within 48 hours (National Institutes of Health Stroke Scale score increase >= 4). This study will provide us with powerful guidance for the treatment of acute LVO stroke with different aetiologies. Ethics and dissemination This study protocol was approved by the Ethics Committee on Human Experimentation at Shandong Provincial Hospital Affiliated to Shandong First Medical University (approval number: SWYX:2022-1025). All the participating sites have received the ethics approval. The outcomes will be disseminated through national and international presentations and peer-reviewed publications. Trial registration number ChiCTR2200065172.