OBJECTIVES: Extended prophylaxis with a low molecular weight heparin (LMWH) such as enoxaparin in high risk surgical patients is consistent with the recommendations made by the American College of Chest Physicians 8th Conference on Antithrombotic and Thrombolytic Therapy. The objective of this study was to compare the costs and effectiveness of extended versus non-extended prophylaxis from the perspective of Australian public hospitals. METHODS: A decision-analytic model was constructed using local treatment algorithms and populated with clinical trial data. A hypothetical cohort of 1000 high-risk general surgery patients received enoxaparin 40mg daily for 7 days (non-extended prophylaxis) or enoxaparin 40mg daily for 28 days (extended prophylaxis) in an Australian public hospital.  Efficacy data were drawn from the ENOXACAN II trial (Bergqvist et al, 2002).  The modelled simulation estimated the incidence of VTE (symptomatic deep vein thrombosis [DVT] and pulmonary embolism [PE]) and adverse events (heparin-induced thrombocytopenia [HIT], post-thrombotic syndrome [PTS], prophylaxis and treatment-related bleeding, mortality) within 28 days and one year of initiating prophylaxis.  RESULTS: By extending prophylaxis with enoxaparin from 7 days to 28 days in 1000 patients, the model estimated 20 fewer symptomatic DVTs, 4 fewer symptomatic PEs, 3 fewer deaths, 10 fewer episodes of PTS and 140 fewer hospital days.  Extending prophylaxis was associated with cost savings of $126,242 from the perspective of an Australian public hospital. CONCLUSIONS: Extended prophylaxis with enoxaparin 40mg represents a cost-effective treatment option for high-risk general surgery patients in Australia.