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It remains unclear whether patients presenting with large vessel occlusion strokes and mild symptoms benefit from thrombectomy.To compare outcomes of endovascular therapy versus medical management in patients with large vessel occlusion strokes and National Institute of Health Stroke Scale (NIHSS) score ≤5.This was a retrospective analysis combining two large prospectively collected datasets including patients with (1) admission NIHSS score ≤5, (2) premorbid modified Rankin Scale (mRS) score 0–2, and (3) middle cerebral-M1/M2, intracranial carotid, anterior cerebral or basilar artery occlusions. Groups receiving (1) endovascular treatment and (2) medical management were compared. The primary and secondary outcome measures were NIHSS shift (discharge NIHSS minus admission NIHSS) and the rates of mRS 0–2 at discharge and 3–6 months, respectively. Univariate, multivariate, and matched analyses were performed.Eighty-eight patients received medical management and 30 thrombectomy. Multivariable analysis indicated thrombectomy was the only predictor of favorable NIHSS shift (β −3.7, 95% CI −6.0 to −1.5, p=0.02), as well as independence at discharge (β −21.995% CI −41.4to −20.8, p<0.01) and 3–6-month follow-up (β −21.1, 95% CI −39.1 to −19.7, p<0.01). A matched analysis (based on age, baseline NIHSS and intravenous tissue plasminogen activator use) produced 26 pairs. Endovascular therapy was statistically associated with lower NIHSS at discharge (p=0.04), favorable NIHSS shift (p=0.03), and increased independence rates at discharge (p=0.03) and 3–6-month follow-up (p=0.04).In patients presenting with minimal stroke symptoms (NIHSS score ≤5) and large vessel occlusion strokes, mechanical thrombectomy appears to be associated with a favorable shift of NIHSS at discharge, as well as higher rates of independence at discharge and long-term follow-up. Confirmatory prospective studies are warranted.