To explore the preventive effect of dl-3-n-butylphthalide (NBP) on early seizures in patients of acute ischemic stroke. Methods: This study retrospectively analyzed data from 1 046 patients with acute ischemic stroke. Patients were divided into groups NBP(n=548) or control(n=462) based on whether received NBP treatment. The two groups were compared for differences in morbidity of early seizures occurring within 14 days of acute ischemic stroke. Multivariable logistic regression analysis was applied to analyze risk factors of early seizures after acute ischemic stroke. Results: The morbidity of early seizures after acute ischemic stroke in the NBP group was significantly lower than that of the control group (3.4% vs. 5.6%, P=0.030). Massive cerebral infarct size (OR=3.451, 95%CI 1.742~8.160, P=0.007), NIHSS score on admission being≥15 points (OR=3.002, 95%CI 1.521~6.872, P=0.013), and lobar infarct location (OR=2.030, 95%CI 1.143~3.482, P= 0.021) were risk factors of early seizures after acute ischemic stroke, whereas receiving NBP treatment (OR= 0.672, 95%CI 0.461~0.870, P=0.033) was a protective factor for early seizures. Conclusion: NBP could effectively prevent early seizures in patients of acute ischemic stroke.