Haemophilia treatment is very expensive and therapy has to be life-long. In comparison with other diseases - e.g., diabetes - haemophilia is rare occurring in approximately 1:10,000. OBJECTIVE: To determine the incremental cost-effectiveness of prophylactic treatment compared with on-demand treatment in patients with haemophilia over a 1 -year period from the third-party payers' perspective. METHODS: A decision-tree model was developed to compare clinical outcomes, quality-adjusted life years, and costs of prophylactic vs. on-demand treatment for three European countries: Germany, Sweden, and the United Kingdom. The time horizon of the decision-analytic model was one year. Health effects were presented in terms of quality-adjusted life years gained (QALYs) and in avoided bleeds as clinical outcome. RESULTS: A total of 506 patients were included. Incremental cost-effectiveness ratio (ICER) for prophylactic treatment in one year for HIV-infected patients younger than 30 years ranged from €1.24 million/QALY (Germany) to €1.73 million/QALY (United Kingdom). For Sweden, the ICER could not be calculated, because all patients younger than 30 received prophylactic treatment. For HIV-negative patients younger than 30 years, ICER ranged from €2.21 million/QALY (Germany) to €3.10 million/QALY (UK). These values were higher than in the HIV-infected group, because the incremental effectiveness of prophylactic treatment was smaller in HIV-negative patients. In patients older than 30 years, ICERs were even higher in HIV-negative patients, ranging from €4.77 million/QALY (Germany) to €5.7 million/QALY (Sweden and UK). In HIV-infected persons older than 30, on-demand treatment dominates prophylactic treatment. Prophylactic treatment was more expensive but yielded slightly lower QALY values. CONCLUSION: Based on our analysis and within the limitations of our short-term model, prophylactic treatment has an extremely high cost-effectiveness ratio when only a 1-year time horizon is considered. Further research should focus on the long-term consequences of the examined strategies.