OBJECTIVES: To compare the cost-effectiveness of extended antithrombotic prophylaxis using low-molecular-weight heparin (LMWH), warfarin or aspirin with no extended prophylaxis following total hip arthroplasty in terms of incremental cost per life year gained. METHODS: Health benefits of extended antithrombotic prophylaxis, measured as the reduction in symptomatic venous thromboembolic (VTE) events and deaths for each treatment alternative, were determined through a meta-analysis of the literature. Potential years of life lost per VTE death was based on mean life years remaining for the age distribution of all patients undergoing total hip arthroplasty in Canada in 2003. Costs included retail drug costs, administration and monitoring costs of extended prophylaxis and costs of diagnosing and managing VTE or bleeding events developing within three months of surgery. The economic analysis used probabilistic modeling structured around a decision tree characterizing extended prophylaxis choices following total hip arthroplasty. RESULTS: No studies reported a statistically significant effect for aspirin so it was excluded from the reference scenario. The reference scenario assumes 50 percent of LMWH and warfarin patients require home visits for injections or INR monitoring. Probabilistic simulations found positive life years (LY) gained in the LMWH and warfarin cohorts relative to no extended prophylaxis (LMWH=6.9 LY gained per 1000 treated; warfarin=5.5/1000). Net treatment costs were highest in the LMWH cohort at US$742,983 per 1,000. LMWH costs were extremely sensitive to the proportion of the cohort receiving home care. Net costs with warfarin were US$70,540 per 1,000 and were much less sensitive to home visit proportions. The incremental cost-effectiveness ratio (ICER) of warfarin relative to no further prophylaxis is US$12,778 per LY gained, while LMWH relative to warfarin is US$475,159. CONCLUSIONS: The cost-effectiveness of warfarin is quite favourable relative to generally accepted thresholds. LMWH is beyond what would be considered cost-effective, even at the lowest home care proportions.