OJECTIVES: Patients undergoing hip fracture surgery are at high risk for postoperative venous thromboembolism (VTE) with the risk remaining elevated for several weeks. Fondaparinux, the new synthetic selective factor Xa inhibitor, is highly efficacious and well-tolerated when administered for 1 week. Extending prophylaxis for 4 weeks results in an additional reduction in symptomatic VTE (relative risk reduction 89%, p = 0.02). This significant efficacy benefit must be weighed against the added cost of prophylaxis for this period. This study examines the cost-effectiveness of extending prophylaxis with fondaparinux from 1 to 4 weeks among patients undergoing hip fracture surgery. METHODS: A cohort simulation model was developed to compare the outcomes and costs to the UK National Health Service (NHS) of extending prophylaxis with fondaparinux for 4 weeks compared with 1 week, up to 5 years. Probabilities for efficacy and safety outcomes were derived from randomized clinical trials with fondaparinux, and from a literature review. Outcomes were symptomatic VTE events (deep-vein thrombosis, pulmonary embolism), recurrent VTE, post thrombotic syndrome and death. Resource consequences were estimated from a survey of UK hospitals and a panel of clinical experts. Costs were based on mean national costs to the NHS. Cost per life-year saved was calculated. RESULTS: Among a cohort of 10,000 patients the use of fondaparinux for 4 weeks compared with 1 week is estimated to prevent an additional 343 symptomatic VTE at 3 months, of which 137 would have been fatal. The number needed to treat to avoid an additional symptomatic VTE event is 30. At 5 years the incremental cost per patient would be £108 and the cost per life year saved £1099. CONCLUSIONS: Extending thromboprophylaxis with fondaparinux from 1 to 4 weeks following hip fracture surgery appears to be a cost-effective strategy with greater clinical benefits achieved and limited additional costs incurred.