For a study, researchers sought to compare the functional and safety outcomes of endovascular thrombectomy (EVT) against medical treatment (MM) in patients with M2 blockage and look into the relationship between perfusion imaging mismatch and stroke severity. In a pooled, patient-level analysis of 3 randomized controlled trials (EXTEND-IA, EXTEND-and IA-TNK parts 1 and 2) and 2 prospective nonrandomized studies (INSPIRE and SELECT), investigators compared EVT with medical management in isolated M2 occlusions for 90-day functional independence (modified Rankin Scale [mRS]=0–2) overall and in subgroups by mismatch profile status and stroke severity. The baseline median (interquartile range [IQR]) National Institutes of Health Stroke Scale (NIHSS) in EVT was 13 (8–19) versus 10 (6–15) in MM, p<0.001. The ischemic core volume before treatment did not differ (EVT=10 [0–24] ml versus MM=9 [3–21] ml, p=0.59). Compared to MM, EVT was associated with a higher rate of functional independence (68.3 vs 61.6%, adjusted odds ratio [aOR] = 2.42, 95% CI=1.25–4.67, p=0.008, inverse probability of treatment weights [IPTW]-OR = 1.75, 95% CI=1.00–3.75, p=0.05), a shift toward better mRS outcomes (adjusted cOR = In patients with a perfusion mismatch profile, EVT was linked to greater functional independence (EVT=70.7% vs MM = 61.3%, aOR=2.29, 95% CI=1.09–4.79, p=0.029, IPTW-OR=2.02, 1.08–3.78, p=0.029), whereas there was no difference in those who did not have a mismatch (EVT=43.8% vs MM = 62.7%, p=0.17, IPTW-OR: 0.71, 95% CI=0.18–2.78, p=0.62). As determined by baseline NIHSS over any threshold from 6 to 10, patients with moderate or severe strokes were more likely to have functional independence with EVT. However, there was no difference between groups with milder strokes below these criteria. Compared to MM, EVT was related to better clinical results in individuals with M2 blockage. The link was found largely in patients with a mismatch profile and those who had more severe strokes.