Abstract: Objective To explore the influencing factors of tirzepatide-associated adverse events and to construct risk prediction models based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods Data from the FAERS database from March 2023 to March 2025 were collected, and adverse drug events (ADE) reports related to tirzepatide were extracted. The reporting odds ratio (ROR) analysis technique and the United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA) standardized method were applied for in-depth data mining and detection of risk signals to systematically identify ADE signals. ADEs were standardized and hierarchically classified using the system organ class (SOC) and preferred term (PT) framework of the Medical Dictionary for Regulatory Activities (MedDRA). The predictive value of the target drug for specific ADEs was evaluated using receiver operating characteristic (ROC) curve analysis. Results A total of 14 929 854 ADE reports were included, comprising 53 145 reports for the target drug and 14 876 709 for other drugs. Mining with ROR and MHRA methods yielded 132 valid signals. The top five ADEs by reported count were dosing errors (14 370 cases), injection site pain (7 711 cases), off-label use (6 119 cases), nausea (5 638 cases), and extra dose administration (3 624 cases). The top five signals by strength were injection site coldness (ROR = 103.59), missed dose (ROR = 73.26), injection site injury (ROR = 71.26), product damage (ROR = 50.61), and extra dose administration (ROR = 50.17). The predictive model based on the ROC curve demonstrated the area under the curve (AUC) of 0.958 for tirzepatide-related target ADEs, indicating high predictive value. Conclusion Systematic analysis of ADE reports using ROR and MHRA methods can reveal key risk signals and underlying mechanisms in post-marketing surveillance of tirzepatide.