Most of the existing reports on abdominal compartment syndrome (ACS) deal with pathophysiology, focusing on its clinical picture and course, and knowledge of the histopathological features of ACS is very poor. Since the heart, kidneys and lungs are the organs primarily targeted for injury in multi-organ failure, we investigated the expression of TNFα and apoptosis in tissue specimens of the heart. This retrospective study was conducted at the Department of Forensic Pathology, University of Foggia. A retrospective review of records extending over a period of 4 years, from 1 April 2001 to 31 March 2005, was carried out and all cases subjected to medico-legal autopsy during this period, whose detailed history and case records were available, were the subjects of our study. Over a 4-year period, on 848 cases subjected to medico-legal autopsy, three cases qualified for inclusion into the study. The immunohistochemical study revealed an intensive positive result for TNFα in heart specimens. The TUNEL assay was positive in heart specimens too. The presented study can contribute to elucidate the pathophysiology of fatal ACS and also define efficient markers for future therapeutic approaches suggesting anti-TNFα strategies may be useful in the management of ACS.