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Background Distal vessel occlusions represent about 25–40% of acute ischemic stroke (AIS), either as primary occlusion or secondary occlusion complicating mechanical thrombectomy (MT) for large vessel occlusion. Objective Our aim was to evaluate safety and effectiveness of MT associated with the best medical treatment (BMT) in the management of AIS patients with distal vessel occlusion in comparison with the BMT alone. Methods Retrospective analysis was conducted on AIS patients treated by MT+BMT for primary distal vessel occlusion between 2015 and 2020, and were compared with a historic cohort managed by BMT alone between 2006 and 2015 selected based on the same inclusion criteria. A secondary analysis was conducted using propensity score matching (PSM) including the following: NIHSS, age and treatment with intravenous thrombolysis (IVT) as covariates. Results Of 650 patients screened, 44 patients with primary distal vessel occlusions treated by MT+BMT were selected and compared with 36 patients who received BMT alone. After PSM, 28 patients in each group were matched without significant difference. Good clinical outcome defined as mRS ≤2 was achieved by 53.6% of the MT+BMT group and 57% of the BMT group (OR, 0.87; 95%CI, 0.3–2.4; P=1.00). The mortality rate was comparable in both groups (7% vs 10.7% in MT+BMT and BMT patients, respectively; OR=0.64; 95%CI, 0.1–4; P=1.00). Symptomatic intracranial haemorrhage (ICH) was seen in only one patient treated by MT+BMT (3.6%). Conclusion Mechanical thrombectomy seems to be comparable with the best medical treatment regarding the effectiveness and safety in the management of patients with distal vessel occlusions. References Sarraj A, Sangha N, Hussain MS, et al. Endovascular therapy for acute ischemic stroke with occlusion of the middle cerebral artery M2 segment. JAMA Neurol 2016;73:1291–1296. Saver JL, Chapot R, Agid R, et al. Thrombectomy for distal, medium vessel occlusions: a consensus statement on present knowledge and promising directions. Stroke 2020;51:2872–2884. Ospel JM, Menon BK, Demchuk AM, et al. Clinical course of acute ischemic stroke due to medium vessel occlusion with and without intravenous alteplase treatment. Stroke 2020;51:3232–3240. Disclosure Pr F. Clarencon reports conflict of interest with Medtronic, Guerbet, Balt Extrusion, Penumbra (payment for readings), Codman Neurovascular and Microvention (core lab). Dr N. Sourour is consultant for Medtronic, Balt Extrusion, Microvention, Stock/Stock Options: Medina. The other authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.