Aim: Drug-induced esophageal ulcers are primarily associated with orally administered drugs, although recent studies have suggested an association with parenterally administered drugs, particularly immune checkpoint inhibitors. However, such cases have not been comprehensively analyzed. Identifying potential associations between various drugs and esophageal ulcers using spontaneous adverse event reporting database is beneficial in reducing drug-induced esophageal ulcers. Methods: We conducted a disproportionality analysis using data from the Japanese Adverse Drug Event Report (JADER) database data from April, 2004 to December, 2023. Signals for esophageal ulcers were detected using the reporting odds ratio with a 95% confidence interval. Weibull distribution analysis was performed to determine the time to adverse event onset for drugs showing signals for esophageal ulcers. We analyzed both orally and parenterally administered drugs separately. Results: Signals for esophageal ulcers were detected with 15 orally administered drugs and seven parenterally administered anticancer drugs, including an immune checkpoint inhibitor (pembrolizumab). Weibull distribution analysis revealed that doxycycline and dabigatran etexilate induced the early onset of esophageal ulcers with median onset times of 8 and 12.5 days, respectively. Conclusion: Our comprehensive investigation using the JADER database revealed that the onset of esophageal ulcers was associated not only for orally administered drugs but also for parenteral administered anticancer drugs, including pembrolizumab. Specifically, doxycycline and dabigatran etexilate may induce the early onset of esophageal ulcers. Overall, our findings highlight the need for early interventions with signal-detecting drugs to prevent and manage esophageal ulcers.