Background: Severe middle cerebral artery stroke (MCA) is associated with a high rate of morbidity and mortality. We assessed the hypothesis that patient-specific variables may be associated with outcomes. We also sought to describe under-recognized patient-centered outcomes. Methods: A consecutive, multi-institution, retrospective cohort of adult patients (≤70 years) was established from 2009 to 2011. We included patients with NIHSS score ≥15 and infarct volume ≥60 mL measured within 48 h of symptom onset. Malignant edema was defined as the development of midline brain shift of ≥5 mm in the first 5 days. Exclusion criterion was enrollment in any experimental trial. A univariate and multivariate logistic regression analysis was performed to model and predict the factors related to outcomes. Results: 46 patients (29 female, 17 male; mean age 57.3 ± 1.5 years) met study criteria. The mortality rate was 28 % ( n = 13). In a multivariate analysis, only concurrent anterior cerebral artery (ACA) involvement was associated with mortality (OR 9.78, 95 % CI 1.15, 82.8, p = 0.04). In the malignant edema subgroup ( n = 23, 58 %), 4 died (17 %), 7 underwent decompressive craniectomy (30 %), 7 underwent tracheostomy (30 %), and 15 underwent gastrostomy (65 %). Conclusions: Adverse outcomes after severe stroke are common. Concurrent ACA involvement predicts mortality in severe MCA stroke. It is useful to understand the incidence of life-sustaining procedures, such as tracheostomy and gastrostomy, as well as factors that contribute to their necessity. [ABSTRACT FROM AUTHOR]