The aim of this study is to assess related risk factors and predict early- and late-onset seizure after first-ever stroke. A total of 2474 consecutive patients with initial stroke in China from 1997 to 2007 were retrospectively investigated, in which, 24 clinical and radiological indexes were used for evaluation. Odds ratio (OR) and 95% confidence interval (CI) were calculated by logistic regression. A total of 232 (11.1%) of patients developed seizures during a mean follow-up period of 18 months, with 123 experiencing early-onset and 109 late-onset seizure. The independent risk factors for early-onset seizure were large lesion (OR = 9.36), subarachnoid hemorrhage (OR = 5.28), initial hyponatremia (OR = 2.10), and cortical involvement (OR = 1.33). The independent risk factors for late-onset seizure were cortical involvement (OR = 11.84) and large lesion (OR = 1.87). These results demonstrated that the risk factors for early seizure after stroke are large lesion, subarachnoid hemorrhage, and cortical involvement. Surprisingly, hyponatremia also predicts seizure in stroke patients. Cortical involvement is a major risk factor for late-onset seizure after stroke.