OBJECTIVES: To evaluate the cost effectiveness of the low-molecular-weight heparin enoxaparin 40 mg once daily (ENOX) relative to no pharmacological prophylaxis (NPP) and to unfractionated heparin 5000 IU thrice daily (UFH) in the prevention of venous thromboembolic events (VTE) in immobilized acutely ill general medical inpatients from the hospital perspective in Germany. METHODS: The incremental cost-effectiveness ratios 'additional cost for ENOX per clinical VTE averted versus NPP' and 'additional cost for ENOX per episode of severe bleeding (ESB) averted versus UFH' were quantified using a modelling approach based on decision-tree technique. Resource use during thromboprophylaxis, diagnosis, and treatment was collected from a hospital survey. Costs were exclusively those to hospitals and were determined by multiplying utilised resource items by the price or tariff of each item. Clinical effectiveness was taken from the MEDENOX [Samama et al. NEJM 1999] and Thromboembolism-Prevention in Cardiac or Respiratory Disease With Enoxaparin [Kleber et al. Am Heart J 2003] trials and from a meta-analysis [Mismetti et al. Thromb Haemost 2000]. The evaluation encompassed 8 (6-14) days of thromboprophylaxis plus time to treat VTE and ESB in hospital. RESULTS: The base-case analysis revealed incremental cost of €1543 for ENOX per clinical VTE averted versus NPP, whereas ENOX dominated UFH. In comprehensive sensitivity analyses, using impact analysis and Monte Carlo simulation, the robustness of the model was shown. In no case had the price of ENOX the main impact on cost effectiveness. In 95% of 10,000 simulation steps, incremental cost for ENOX ranged between €201 and 4€154 per clinical VTE averted versus NPP. In 91% of 10,000 simulation steps, ENOX remained dominant over UFH. CONCLUSIONS: In acutely ill general medical inpatients, ENOX offers hospitals in Germany a highly cost-effective thromboprophylaxis compared to NPP and an enormous saving potential when used instead of UFH.