Peroxiredoxins (Prx) are a family of antioxidant thioredoxin or glutathione-dependent peroxidases. The major functions of Prx are the modulation of signaling cascades that apply hydrogen peroxide (H2O2) as a second messenger molecule, and cellular protection against oxidative stress. We investigated the expression of Prx isoforms 1–6 in human non-failing (NF, donor hearts, n=6, male, age: 53.3±2.1 yrs) and failing myocardium (DCM, orthotopic heart transplantation, dilated cardiomyopathy, n=15, male, 57.0 ± 1.7 yrs). The protein expression of Prx 1-2 was similar in NF and DCM. The protein expression of Prx 3–6 and the mRNA-expression of Prx 4 were decreased in DCM. Immunohistochemical analyses provided evidence that all Prx isoforms were present in cardiomyocytes and endothelial cells, whereas Prx 1 and 2-staining was more pronounced in endothelial cells, prx 3–5 were similarily distributed between endothelial cells and cardiomyocytes. Prx6 staining was more prominent in cardiomyocytes. Conclusions. Prx are differentially regulated in DCM. The selective downregulation of cardiac isoforms suggests, that there is a dysregulation of the radial homeostasis in DCM. Thus, therapeutic interventions on the proteins involved in the regulation of oxidative stress may be a future aim for the treatment of heart failure patients.