Patients suffer preventable harm from their medical treatment. The traditional approaches to investigating medical treatment related deaths are the 'hospital mortality audit' and legal or coroners investigation. The aim is to describe how the patient safety movement in the late 1990s is changing traditional approaches to the investigation. The prevention of medical treatment related death involves an investigation as one of five major stages. These are Stage I Preparedness; Stage II Recognition and reporting; Stage III Investigation and analysis; Stage IV Findings and recommendations; and Stage V Response. The influence of the patient safety approach is considered at each stage with a particular focus on Stage I. It is at this stage that the concepts of clinical governance, culture and systems of care have a major influence on the nature of an investigation. The genesis of the modern forensic investigation into medical treatment related deaths in Victoria, Australia is described. The formation of the Clinical Liaison Service incorporates concepts from the patient safety approach with clinical staff to transform the traditional Coroner's investigation. Benefits of a modern forensic investigation include improving appropriateness of cases proceeding to investigation and a focus on prevention. Achieving a reduction in medical treatment related death requires substantial shifts towards an approach consistent with the patient safety.