To determine differences in 90-day mortality and identify risk factors among different etiological classifications of ischemic stroke using the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification.Our retrospective analysis included 538 ischemic stroke patients. The cause of stroke was categorized according to the TOAST criteria, and 90-day mortality rates were obtained through the patient follow-up. Age, sex, previous medical history, and clinical features were used in the analysis of potential risk factors.There were 38 deaths during the 90-day follow-up period. Patients in the undetermined cause subgroups experienced significantly higher mortality rate than those in subgroups with small artery occlusion and large artery atherosclerosis. Factors independently associated with 90-day mortality for patients with the large artery atherosclerosis stroke subtype were age (95% confidence interval [CI], 1.010–1.192, P = .028), history of hypertension (95% CI, 3.030–99.136, P = .001), high blood glucose (95% CI, 1.273–2.354, P < .001), high cholesterol (95% CI, 0.017–0.462, P = .004), high uric acid (95% CI, 2.360–64.389, P = .003), and National Institute of Health Stroke Scale(95% CI, 1.076–1.312, P = .001). Age (95% CI, 1.012–1.358, P = .034) and high cholesterol (95% CI, 0.011–0.496, P = .007) were independently associated with 90-day mortality for patients with the small artery occlusion subtype of stroke.Our analysis identified that certain risk factors and 90-day mortality differ significantly among different stroke subtypes, as classified by the TOAST criteria. These risk factors must be considered carefully to provide the best clinical management of these patients and thus reduce mortality.