OBJECTIVES: Dabigatran etexilate (DBG) is a new oral direct thrombin inhibitor for prophylaxis of venous thromboembolism (VTE) in patients who have undergone total hip replacement (THR) or total knee replacement (TKR) surgery. Advantages of DBG over parenteral prophylaxis might include but are not limited to reduced resource use for 1) teaching patients to self-inject; 2) home-care visits for parenteral administration; and 3) absence of Heparin Induced Thrombocytopenia (HIT). Based on proven non-inferiority, the aim of this study was to conduct a cost-minimization analysis of oral DBG versus parenteral low-molecular weight heparin (LMWH) and Fondaparinux formulations from the perspective of the Dutch National Health Service. METHODS: A retrospective cohort study was conducted to measure resource use associated with parenteral prophylaxis. Drug-utilization data were combined with local unit costs. Probabilistic sensitivity analysis was performed to account for uncertainty around relevant parameters included. RESULTS: Home-care visits for parenteral administration problems were required by 9.9% (95%CI: 6.4–13.4) and 9.6% (95%CI: 5.8–13.4) of THR and TKR patients, respectively. Based on costs for 1000 patients treated with DBG versus LMWHs, per patient cost-savings with DBG were estimated at €24.63 (95%CI: -0.56–54.19) and €18.39 (95%CI: -2.54–41.52) for THR and TKR, respectively. The probability that DBG would be cost-saving is 97.1% and 95.6% for THR and TKR, respectively. These cost-savings were even higher when including Fondaparinux with per patient cost-savings of €84.87 (95%CI: 58.04–117.64) and €33.41 (95%CI: 12.27–57.36) for THR and TKR, respectively. Separate calculations for DBG versus Nadroparin and Dalteparin in THR resulted in a probability of achieving cost-savings with DBG of 19.0% and 100%, respectively. For TKR these probabilities for DBG versus Nadroparin and Dalteparin were estimated at 37.0% and 100%. CONCLUSIONS: Thromboprophylaxis with DBG is cost-saving in patients undergoing THR/TKR for the perspective of the Dutch National Health Service.