Objectives. To investigate adverse events (AEs) associated with upadacitinib in the real world using data mining from the FDA Adverse Event Reporting System (FAERS). Methods. Disproportionality analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multiitem gamma Poisson shrinker (MGPS) algorithms, was used to quantify the signals of upadacitinib-associated AEs. Results. The study found 23683 reports of AEs associated with upadacitinib. A total of 149 substantial disproportionality preferred terms (PTs) that complied with all algorithms were identified. The infections discovered matched those mentioned in the specification and clinical trials, including pneumonia, upper respiratory tract infection, herpes zoster, and acne. Malignant and thrombotic AEs were also noted. Diverticulitis, myocardial infarction, transient ischaemic attack, and dysstasia were among the new AEs found. Upadacitinib-related AEs had a median onset time of 237 days and an interquartile range (IQR) of 78-509 days. Conclusions. The findings of our study were in line with clinical observations, and we also identified potential novel and unexpected AEs signals for upadacitinib, indicating the necessity for prospective clinical trials to corroborate these findings and demonstrate their link. Our results offered significant support for additional upadacitinib safety research.