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Introduction: Ischemic strokes (IS) are the leading cause of seizure development in the elderly and recent reports associate post-IS seizures with increased morbidity and mortality. Yet, there is a scarcity of studies defining the role of anticonvulsant prophylaxis in the prevention of seizures after IS. As a result, AHA/ASA guidelines do not recommend the prophylactic administration of anticonvulsants in this setting. Here, the ability of newer generation anticonvulsants, mainly levetiracetam, to prevent post-IS seizures is analyzed.Methods: We performed a review of our clinical database from 2010-2015 including patients that suffered IS. Patient demographics, seizure incidence, and functional outcomes were collected. Patients that received prophylaxis and those who did not were divided. Logistic regression and quantile regression models assessed relationships between outcomes and risk factors, each analysis was corrected for age, gender, and initial NIH stroke scale (NIHSS) score.Results: From a total of 1771 patients included in this study, the mean age was 69 and 51.1% were male. Median initial NIHSS score was 6.0 (IQR, 2-14), with prophylaxis and 3.0 (1.0-7.0) without. Of the 534 patients that had prophylactic anticonvulsants, 352 (65.9%) first received levetiracetam and 127 (23.8%) received gabapentin. Those with prophylaxis had 36 (6.7%) seizures and without experienced 47 (3.6%). Despite correcting for the initial severity of stroke, prophylaxis independently and significantly increased the odds of a seizure (adjusted OR, 1.76; 95% CI, 1.09-2.87; p=0.02). Furthermore, prophylaxis was associated with an increased discharge NIHSS score (adjusted difference, 1.0; 95% CI, 1.0-1.0; p<0.001) but not an increase in mRS score at discharge. Patients with prophylaxis also had longer hospital stays (adjusted difference, 1.0 days; 95% CI, 0.7-1.3, p<0.001) and higher total hospital costs (adjusted difference, $9,103; 95% CI, 5,707-12,498; p<0.001).Conclusions: Post-IS anticonvulsant prophylaxis is not associated with improved outcomes or a reduced seizure incidence. Instead, prophylaxis here was associated with an increased odds of having a seizure after IS, a worse NIHSS score at discharge with longer hospital stays and higher costs.