Chronic Chagas' disease cardiomyopathy (CCC) is an often-fatal outcome of Trypanosoma cruzi infection, having shorter survival than the clinically similar idiopathic dilated cardiomyopathy (IDC). In order to analyze the molecular changes in the affected myocardium, we used proteomic approach to draw a high-resolution protein expression profile in CCC heart samples and compare it to IDC samples. Homogenates of left ventricular samples from end-stage CCC and IDC hearts explanted during heart transplantation were subjected to bidimensional electrophoresis. Coomassie blue-stained protein spots were selected with imaging software, and then were excised and subjected to tryptic digestion by processing in a robotic workstation. Protein identification was performed by peptide mass fingerprinting with the aid of MALDI-ToF mass spectrometry and virtual tryptic digestion of proteins in sequence databanks. We identified 319 proteins (112 distinct proteins), corresponding mainly to structural and mitochondrial proteins and also proteins of low expression such as transcriptional factors, and related with immune response, apoptosis and stress process. Differential CCC/IDC protein expression analysis identified significantly reduced expression of proteins related with the energetic metabolism, such as creatine kinase, aconitase and ATP synthase, in the myocardium of a CCC patient, as compared to a paired IDC patient. We also observed a higher expression of vimentin in the CCC sample, while the IDC sample showed some actin isoforms that are not present in IDC sample. The identification of a high number of proteins involved with apoptosis, oxidative stress and immune response reinforce the importance of these processes on the pathogenesis of CCC. Furthermore, the energetic deficit found in CCC heart could be related to the shorter survival observed in CCC as compared with IDC. Supported by: FAPESP and CNPq.