OBJECTIVES: Churg-Strauss Syndrome (CSS) is rare autoimmune condition characterized by vasculitis and myocarditis. There have been cases of eosinophilic myocarditis in patients using leukotriene-receptor antagonists (LTRA); however no pharmacovigilance analysis was conducted to characterize this potential signal. METHODS: Adverse event reports submitted to the FDA Adverse Event Reporting System between 1997 and 2014 were analyzed to detect signals of non-infectious myocarditis in relation to treatment with LTRA. Empirical Bayes Geometric Mean (EBGM) with corresponding 95%CI was calculated. The following MedDRA Preferred Terms (version 18.0) represented the outcome of interest: “allergic myocarditis”; “autoimmune myocarditis”; “eosinophilic myocarditis”; and “myocarditis”. Generic names were used to represent LTRA. RESULTS: Totally, 39 myocarditis reports were submitted for LTRA, corresponding to montelukast (n=27) and zafirlukast (n=12). Both products were associated with significant signals for myocarditis (montelukast: EBGM=3.29, 95%CI=2.38-4.46; zafirlukast: EBGM=18.4, 95%CI=8.14-31.8). Majority of LTRA users were females with mean age (SD) 50.2 years (16.2) for montelukast and 42.8 years (15.8) for zafirlukast. All reported myocarditis events were serious, with 5 fatalities (montelukast, n=2; zafirlukast, n=3); 12 life-threatening (montelukast, n=7; zafirlukast, n=5); and 31 hospitalizations (montelukast, n=21; zafirlukast, n=10). Only 15% of patients were on LTRA monotherapy. On average, LTRA users were using 4 concurrent medications at the time of myocarditis occurrence. CONCLUSIONS: Myocarditis and CSS could be consequences of LTRA therapy, which is mechanistically plausible; however signal evaluation is required, especially to account for concurrent medications and the severity of underlying inflammatory condition for which LTRA was prescribed, e.g. asthma.