OBJECTIVES:  Antiepileptic drugs (AEDs) sales have been increasing globally. The US Food and Drug Administration (FDA) and Health Canada (HC) are two regulatory agencies that use different approval processes and regulatory actions to approve new drugs. The aim of this study was to conduct a comparative analysis of antiepileptic drugs (AEDs) approved in the peirod 1953- 2016 by these two regulatory agencies. METHODS:  In the study period, all AEDs approved by the FDA and HC were collected from the Drugs@FDA database, the Health Canada Drug Product database, and the Health Canada Notice of Compliance (NOC) database. For each AED, the following data were extracted: approval date, indications, contraindications, dosage forms, routes of administration, strengths, boxed warnings, market status and review status. Differences in these characteristics were assessed qualitatively and quantitatively. RESULTS:  Of the 46 drugs on the WHO ATC list, 13 AEDs were never submitted to or approved by the FDA and HC; 33 AEDs were approved by either the FDA or HC. Only 19 AEDss were approved by both regulatory agencies. The mean number of AEDs’ indications approved by the FDA (1.95±0.97) was higher than the HC’s (1.63±0.83), though the difference was not statistically significant. The FDA approved more indications in 7 AEDs (36.8%) while HC approved more indications for only one drug. The average number of contraindications approved by HC (2.89±2.77) was higher than the average number of contraindications approved by the FDA (1.53±1.54). Other differences were identified in drug approval dates, restrictions, limitations, boxed warning, dosage forms, and strengths. CONCLUSIONS:  There are significant differences in AEDs characteristics approved by the FDA and HC. More research may be needed to compare the clinical evidence that lead to these discrepancies between the two regulatory agencies.