Objective To investigate the influencing factors for post-stroke early-onset epileptic seizures and the effect of treatment in the acute stage of stroke on incidence rate. Methods The patients hospitalized in our hospital from September 2014 to February 2017, who developed ischemic stroke for the first time and had no history of epilepsy, were selected. The patients were enrolled according to admission medical records and telephone follow-up, and related clinical data were collected. Logistic regression was used to evaluate the influencing factors for post-stroke early-onset epileptic seizures and the effect of treatment in the acute stage of stroke. Results A total of 1224 patients were enrolled, among whom 28 (2.3%) had post-stroke early-onset epileptic seizures. The univariate analysis showed that there were significant differences between the two groups in TOAST type, National Institutes of Health Stroke Scale score, cortex involvement, and administration of drugs during the acute stage (antiplatelet drugs, statins, and antihypertensive drugs) (P<0.05). The multivariate logistic regression analysis showed that cortex involvement (odds ratio[OR]=2.494, 95% confidence interval[CI]:1.094-5.686, P<0.05) and the use of antiplatelet drugs (OR=0.177, 95% CI:0.047-0.657, P<0.05), statins (OR=0.145, 95% CI:0.051-0.418, P<0.05), and antihypertensive drugs (OR=0.337, 95% CI:0.123-0.921, P<0.05) in the acute stage were associated with post-stroke early-onset epileptic seizures. Conclusions Patients with ischemic stroke with cortex involvement tend to develop post-stroke early-onset epileptic seizures. The administration of antiplatelet drugs, statins, and antihypertensive drugs in the acute stage of ischemic stroke may reduce the incidence rate of post-stroke early-onset epileptic seizures.