Introduction: Despite randomized trials demonstrating the benefit of endovascular therapy (EVT), large artery occlusion (LAO) acute ischemic stroke (AIS) remains associated with high mortality. Identifying factors associated with mortality for patients presenting with LAO AIS can assist in therapeutic decision-making and prognostication. Hypothesis: Among patients with LAO AIS, factors associated with 90-day mortality include older age, higher presenting NIHSS score, and lower final Thrombolysis in Cerebral Infarction (TICI) score. Methods: From November 2016 to April 2019, we conducted a retrospective analysis from a large healthcare system’s stroke network registry of patients presenting with ICA and/or MCA occlusions. Ninety-day mortality status from registry follow-up was corroborated with the Social Security Death Index. A multivariable logistic regression model was fitted to determine demographic and clinical characteristics associated with 90-day mortality. Results: Among 796 patients with 800 encounters, mean age was 68 years, 52% were women, mean presenting NIHSS was 14, and 97% presented within 24 hours of last known well time. Fifty-one percent were treated with EVT. Mortality rate for the entire cohort was 25%. In a univariate analysis, there were significant differences in age, gender, race, blood glucose, presenting NIHSS, hypertension, atrial fibrillation, CTP core volume, CTP delayed perfusion volume, EVT treatment, number of passes for EVT, final TICI score, and discharge mRS, between patients with and without 90-day mortality. In the multivariable model, increasing age (per 10 years, OR 1.54, 95% CI 1.20, 1.97) and higher discharge mRS (per 1 point, OR 4.47, 95% CI 3.05, 6.55) were associated with 90-day mortality. Female gender (OR 0.57, 95% CI 0.27, 1.18) and final TICI score of 2B or better (OR 0.42, 95% CI 0.18, 1.01) were protective against 90-day mortality. Conclusions: Increasing age and worse discharge functional outcome are associated with 90-day mortality after LAO AIS. Female gender and better revascularization after EVT are associated with lower mortality. Additional studies are required to refine mortality outcome prediction models for patients presenting with LAO AIS.