Sudden Infant Death Syndrome (SIDS) has been reported to be the leading cause of death in infants under 1 year of age in many countries. Unfortunately, a paucity of published research data exists in South Africa, with regard to the incidence of and investigation into the circumstances surrounding Sudden Unexplained Deaths in Infants (SUDI) and/or SIDS. Currently, even though most academic centers conform to a protocol consistent with internationally accepted standards, there exists no nationally accepted infant death investigation protocol in South Africa. It is the aim of this study to review the current practice of infant death investigation in two representative but geographically and demographically distinct centers. Retrospective case audit over a five-year period (2000-2004) was conducted at two large medico-legal mortuaries in Pretoria (Gauteng) and Tygerberg (Cape Town). Case files on all infants younger than 1 year of age were reviewed. The outcome measures included number of deaths, demographic details and the nature and final outcome of the post mortem examinations. A total of 512 cases were identified as possible SIDS cases and of these, 171 was classified as SIDS. The study showed marked inter-case and inter-divisional variation in terms of the investigation of infant deaths at the two institutions. It is envisaged that this study will focus attention on the current lack of usable data regarding sudden/unexplained/unexpected infant deaths in South Africa, and aid in the formulation and implementation of a practical (yet internationally accountable) infant death investigation protocol, which could facilitate comparisons with other countries and initiate further structured research in this field.