Introduction: Endovascular Therapy (EVT) has become standard care for selected acute ischemic stroke (AIS) patients with a proximal emergent large vessels occlusion (ELVO), such as occlusion in terminal ICA or M1 of MCA. It is not uncommon to have a M2 occlusion producing an unfavorable outcome; however, the data on EVT in AIS with M2 occlusion is limited. We sought to explore the clinical features, efficacy and safety of EVT in M2 occlusions. Methods: AIS patients with an ELVO who underwent EVT in a single academic center from January 2016 to May 2018 were consecutively included in our quality assurance database. The clinical characteristics, procedural features and clinical outcome were compared between M2 and M1/ICA occlusions using a t-test (Wilcoxon Test) and Fisher Exact Test. Results: Among 239 AIS patients, of which 43.9% were male, who received EVT, 179 patients had a M1 or ICA occlusion and 60 had a M2 occlusion. Compared with a M1/ICA occlusion, those with a M2 occlusion were older (age 74±13 vs 69±15 year old, p = 0.01), had a higher ASPECTS (median 9 vs 8, p = 0.012), and a lower NIHSS score (median 16 vs 19, p=0.01). These cohorts had a similar number of EVT passes (2.6 vs 3.0, p = 0.25) and time interval from last known well to groin puncture and final recanalization. Patients with a M2 occlusion had a trend of lower post-operative hemorrhage rate (including ICH and SAH, 24.1% vs 36.3%, p = 0.11) and a lower NIHSS at discharge (median 4 vs 9, p = 0.013). The day 90 mortality rate (14.3% vs 25.9%, p = 0.11) and favorable outcome (mRS = 0-2) rate (40.8% vs 33.3%, p = 0.39) were similar in patients with a M2 vs M1/ICA occlusion. Conclusion: EVT of M2 occlusions is feasible with a similar rate of post-procedural complications and favorable outcome as M1/ICA occlusions. Further trials are needed to demonstrate the efficacy of EVT in comparison to medical management for AIS patients with a M2 occlusion.