Bone marrow transplantation (BMT) in young children improves results in β-thalassemia major. Graft versus host disease (GVHD) is an important complication of peripheral blood stem cell transplantation. GVHD affects heart with a behavior resembling an autoimmune disease, including pericardial effusion. We describe a 22-year-old β-thalassemia major patient who underwent bone marrow transplantation with an HLA-identical sibling donor. The patient didn't have any serious problem until 15 months after transplantation. He presented with chest discomfort and progressive dyspnea. Early echocardiogram showed mild pericardial effusion. Four days later, the effusion had increased, impending to cardiac temponade requiring pericardectomy. Immunospressive drugs and pericardectomy resulted in significant improvement in ventricular filling. Cardiac cGVHD, an un-common complication of HSCT may be presented as pericardial effusion. Although early initiation of steroids is very important, heart monitoring is necessary to diagnose cardiac temponade.