BACKGROUND: Previous studies have explored the association between levetiracetam (LEV) and severe cutaneous adverse reactions (SCARs). However, most investigations have relied on clinical trial data or case reports from individual medical centers. Consequently, the precise relationship between LEV and SCARs in real-world settings remains elusive. RESEARCH DESIGN AND METHODS: Data from the FDA Adverse Event Reporting System (FAERS) and EudraVigilance databases were analyzed, focusing on LEV-associated SCAR events utilizing disproportionality analysis methods. RESULTS: This study identified a significant correlation between LEV and SCARs ( CONCLUSIONS: Despite certain limitations, this study offers updated insights into the association between LEV and SCARs. These findings underscore the significance of monitoring and actively managing LEV-associated SCARs to promote its safe and effective use.