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Background and Purpose: Minor acute ischemic stroke (AIS) patients—defined by an NIHSS score < 6—presenting with proximal middle cerebral artery large vessel occlusions (MCA-LVO) is a subgroup for which treatment is still debated. Although these patients present with minor symptoms initially, studies have shown that several patients afflicted with MCA-LVO in this subgroup experience cognitive and functional decline. Although mechanical thrombectomy (MT) is the standard of care for patients with an NIHSS score of 6 or higher, treatment in the minor stroke subgroup is still being explored. The purpose of this preliminary study is to report our center's experience in evaluating the potential benefit of mechanical thrombectomy (MT) in minor stroke patients when compared to medical management (MM). Methods: We performed a retrospective study with two comprehensive stroke centers within our hospital enterprise of consecutive patients presenting with minor AIS secondary to MCA-LVO (defined as M1 or proximal M2 segments of MCA). We subsequently evaluated patients who received MT versus those who received MM. Results: Between January 2017 and July 2021, we identified 46 AIS patients (11 treated with MT and 35 treated with MM) who presented with an NIHSS score < 6 secondary to MCA-LVO (47.8% 22/46 female, mean age 62.3 years, range 49–75 years). MT was associated with a significantly lower mRS at 90 days (median: 1.0 [IQR 0.0–2.0] versus 3.0 [IQR 1.0–4.0], p = <0.001), a favorable NIHSS shift (−4.0 [IQR −10.0–−2.0] versus 0.0 [IQR −2.0–1.0], p = 0.002), favorable NIHSS shift dichotomization (5/11, 45.5% versus 3/35, 8.6%, p = 0.003) and favorable mRS dichotomization (7/11, 63.6% versus 14/35, 40.0%, p = 0.024). Conclusions: In our center's preliminary experience, for AIS patients presenting with an NIHSS score < 6 secondary to MCA-LVO, MT may be associated with improved clinical outcomes when compared to MM only. [ABSTRACT FROM AUTHOR]