Objective To investigate the risk factors, clinical features and outcomes of patients with large hemispheric infarction (LHI), and explore the association between TOAST classification and LHI. Methods We prospectively registered consecutive cases of acute ischemic stroke at the neurological wards of West China Hospital, Sichuan University from January 1st 2010 to February 29th 2012. We collected the demographic data, risk factors, and other related data, assessed the National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) scores at admission, and followed-up the Modified Rankin Scale (mRS) scores at the third month from the onset. In different TOAST classifications, univariate analysis and multivariate analysis were used to find predictors for the occurrence and prognosis of LHI. Results Of the enrolled 1 729 patients with acute ischemic stroke, 317 (18.3%) had LHI. The multivariate analysis showed that male, hypertension and onset to admission time were the independent predictive factors for the large-artery atherosclerosis type LHI (P<0.05); atrial fibrillation and valvulopathy were the independent predictive factors for cardioembolism type LHI (P<0.05). Meanwhile, age, hypertension, onset to admission time, and NIHSS and GCS scores at admission were the independent predictive factors for death/disability (mRS>3) within three months (P<0.05). Conclusions Hypertension, gender, onset to admission time, atrial fibrillation, and valvulopathy are independently associated with the occurrence of LHI. Young patients with lower GCS, higher NIHSS scores and no hypertension are more likely to have a better prognosis after LHI.