Tirzepatide is a novel drug for the treatment of type 2 diabetes mellitus and chronic weight management, and there is an urgent need to explore its safety profile. The FDA Adverse Event Reporting System (FAERS) database provides a reliable pathway for adverse event (AE) disproportionality analysis. Data regarding AEs registered in the FAERS between Q2 2022 and Q4 2023 were collected for this study. The reporting odds ratio (ROR) method was applied to analyse the association between tirzepatide use and the risk of developing AEs. The occurrence of ≥3 AEs with an ROR value 95% confidence interval (CI) lower limit >1 was considered to indicate statistical significance. Data on 638,153 AEs were collected from the FAERS database, and tirzepatide use was implicated for 8,096 of those AEs. A total of 98 preferred terms (PTs) were detected as positive signals for tirzepatide use. Frequently observed expected AEs included injection site pain, nausea, injection site haemorrhage, diarrhoea, and vomiting. Some unexpected AEs that were frequently observed included incorrect doses, off-label use, the administration of extra doses, an inappropriate schedule of product administration, and increased blood glucose. In this study, we identified potential novel and unexpected AE signals associated with tirzepatide use. Our findings confirm the importance of real-world disproportionality analysis in identifying the safety profile of new drugs, ultimately contributing to the safe clinical application of tirzepatide.