BACKGROUND: Tasimelteon is a novel dual melatonin receptor agonist approved for the treatment of non-24-hour sleep-wake disorder (N24HSWD). The purpose of this study was to provide a comprehensive analysis of post-marketing adverse events (AEs) for tasimelteon by analyzing the U.S. FDA Adverse Event Reporting System (FAERS) database. METHODS: Four algorithms are employed in this study to mine the significant signals: multi-item gamma poisson shrinker (MGPS), Bayesian confidence propagation neural network (BCPNN), reporting odds ratio (ROR), and proportional reporting ratio (PRR). RESULTS: Tasimelteon was the primary suspected drug in 5,125 adverse event reports that were identified between the first quarter of 2014 and the first quarter of 2024. Significant system organ categories (SOC) included psychiatric disorders, general disorders and administration site conditions, and nervous system disorders. We not only confirmed the adverse reactions outlined in the prescribing information such as somnolence, nightmare or abnormal dreams, and inhibitory drug interaction, but also revealed new potential risks that were not documented, such as insomnia and sleep disorder. CONCLUSIONS: This study revealed the characteristics of tasimelteon-associated adverse drug reactions, improved understanding of drug safety, and provided valuable signals for optimizing drug use regimens. Additional large-scale prospective studies remain necessary in the future.