Background: Extracellular traps (ETs) formed by neutrophils (NETs) and eosinophils (EETs) have been described in coronary thrombi, contributing to thrombus stability. A key mechanism during NET formation is histone modification by the enzyme PAD4. Citrullinated histones, the product of PAD4 activity, are often attributed to neutrophils. Eosinophils also express high levels of PAD4 and the contribution of PAD4 to EET formation is not known. Methods: We performed immunohistological analysis of a large, intact and eosinophil-containing coronary thrombus retrieved from the right coronary artery using an aspiration catheter. Moreover, we studied isolated human eosinophils regarding their capability to form PAD4-dependent EETs in response to strong ET-inducing agonists as well as activated platelets and bacteria. Results: Histopathology and immunofluorescence microscopy identified a coronary thrombus rich in platelets and neutrophils, with distinct areas containing von Willebrand factor and intracellular and extracellular citrullinated histone H3 (H3Cit). Eosinophils were also identified in leukocyte-rich areas. The majority of the H3Cit+ signal colocalized with myeloperoxidase, but some colocalized with eosinophil peroxidase exclusively, indicating EETs. Eosinophils isolated from healthy volunteers produced H3Cit+ EETs, indicating an involvement of PAD4 activity. The selective PAD4 inhibitor GSK484 blocked this process, supporting PAD4-dependence of H3Cit+ EET release. Citrullinated histones were also present in EETs produced in response to live Staphylococci . However, limited evidence for EETs was found in mouse models of venous thrombosis or infective endocarditis. Conclusions: As in NETosis, PAD4 can catalyze the formation of EETs. In turn, inhibition of PAD4 decreases EET formation, supporting the future utility of PAD4 inhibitors as possible antithrombotic agents for the coronaries.