<p>Azoles are first-line antifungal agents known to increase the risk of statin-related myopathy due to drug interactions. However, myopathy events have also been observed in patients using azoles without concurrent statin use, suggesting that azoles may be linked to an increased risk of non-statin-related myopathy. Based on data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), this study aimed to determine whether azoles are associated with a disproportionately high incidence of myopathy after excluding statin-related reports and to explore the potential contribution of interactions between azoles and nonstatins. We used Open Vigil 2.1 to conduct a disproportionality analysis based on data from the FAERS from Q1 2004 to Q2 2023. We excluded reports with at least one statin. Myopathy was defined based on a Standardized MedDRA Query (SMQ). Five azoles were screened. The reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) information components (ICs) were used for disproportionality analysis. Subset analysis and the Ω shrinkage measure model were used to detect drug‒drug interaction (DDI) signals. Sensitivity analysis was also conducted. In the nonstatin dataset, we identified 215 cases of myopathy associated with azole use. Notably, 50.5% of the reports involved voriconazole among East Asian patients. Voriconazole, fluconazole, and itraconazole were associated with myopathy in narrow and broad SMQ searches. Posaconazole and isavuconazole were associated with myopathy in the broad SMQ search. Forty-two potential DDIs between azoles and nonstatins were identified. A literature review identified 12 related cases. Azoles, particularly voriconazole in East Asian populations, are associated with an increased reporting frequency of myopathy events in the absence of statin use. DDIs with some nonstatins further elevate this frequency.</p>