OBJECTIVES To evaluate the cost-effectiveness of dabigatran etexilate (DGB) compared to enoxaparin in the prevention of venous thromboembolism (VTE) following total hip replacement (THR) or total knee replacement (TKR) from the perspective of the Portuguese NHS. METHODS DBG (220mg once daily) was compared to enoxaparin (40mg once daily) in patients undergoing THR (prophylaxis 28-35 days) and TKR (6-10 days). A decision tree was used to model the ten week post-surgery acute phase. A Markov process modeled long-term events such as recurrent VTE, post-thrombotic syndrome and intracranial hemorrhage for patient's remaining lifetimes. Relative risks for VTE and bleed events were derived from the DBG phase III trials, RE-NOVATE and RE-MODEL which compared DBG with enoxaparin 40mg once daily. Published longitudinal studies were used to estimate the probabilities of long-term events. Resource use associated with administration of the prophylaxis and the management of clinical events was obtained from a national multi-centre prospective study involving 50 patients. Unit costs were taken from national sources. Utility weights were taken from published international literature. RESULTS VTE and bleeding rates were similar for DBG and enoxaparin. DBG was marginally more expensive than enoxaparin in TKR but less costly in THR, since no nursing time for administration of treatment is required in hospital or following discharge. The probabilistic analysis estimated that DBG cost an additional €11 per patient in TKR (ICER €2,848 /QALY) and saved €255 per patient in THR. The probability of DBG being cost-effective was 79% in TKR and 99% in THR at a willingness to pay threshold of €20,000 per QALY. Results proved to be robust across a wide range of sensitivity analyses. CONCLUSIONS DBG is cost-saving in THR compared to enoxaparin and non-inferior in terms of efficacy or safety. Thus, DBG is cost-effective for the prevention of VTE in patients undergoing THR.