BACKGROUND: Skin ulcer (SU) may increase the risk of systemic infections and have evolved into an important public health problem. However, there is a lack of research specifically on drug-induced SU. RESEARCH DESIGN AND METHODS: We extracted data on adverse drug events (ADEs) associated with SU from the FDA Adverse Event Reporting System (FAERS) database. Disproportionality analysis was performed to calculate the risk signals for drugs that may induce SU. Logistic regression analysis was carried out to investigate the factors influencing the occurrence of SU. RESULTS: 21372 cases of SU were reported in FAERS database between 2005 and 2024. Based on the frequency of ADE reports, we compiled a list of the top 50 drugs associated with SU. Only 15 drugs had explicit mentions of SU in their instructions, while 32 drugs were recognized as positive signals for SU by reporting odds ratio model. Logistic regression revealed the duration of medication was the risk factor for tocilizumab, alendronate sodium, and erlotinib usage. Females were also identified as risk factor for erlotinib. CONCLUSIONS: Our study identified 32 drugs potentially inducing SU, which provides valuable insights for targeted prevention and treatment strategies aimed at mitigating the risk of drug-induced SU.