OBJECTIVES: To evaluate the cost-effectiveness of rivaroxaban and dabigatran compared to enoxaparin as venous-thromboembolism prophylaxis post total hip replacement (THR), from the Irish health payer perspective.  METHODS: A hybrid model combing an acute phase decision tree (180 days post-surgery) and a chronic phase Markov model (patient lifetime) was developed using TreeAge Pro 2008®.  Outcome measures were QALYs and LYGs.  Future costs and outcomes were discounted at 4%. Treatment efficacy and major bleeding probabilities were derived from pivotal clinical trials.  Thromboprophylaxis independent probabilities were identified via a literature search.   A one-way sensitivity analysis of all probabilities was completed using the upper/lower bounds of the 95% confidence interval where available; otherwise point estimates were varied ±50%.  A probabilistic sensitivity analysis (PSA) using second order Monte Carlo simulation was performed.  Probabilities were assigned beta distributions. Dirichlet distributions were adopted for multibranch nodes.  Utilities and direct costs were given beta and lognormal distributions respectively. RESULTS: Basecase Analyses: Rivaroxaban dominated both dabigatran and enoxaparin.  The incremental cost-effectiveness ratios for dabigatran relative to enoxaparin were €1885 per LYG and €1811 per QALY.  One-Way Sensitivity Analysis: The model was robust to all but three probability variations; the probabilities that a proximal deep vein thrombosis (DVT) will occur on dabigatran, a pulmonary embolism or proximal DVT will occur on enoxaparin.   PSA: At a €45,000/QALY threshold, the probability that rivaroxaban was the most cost-effective strategy was 67%, followed by dabigatran (19%) and enoxaparin (14%).    A cost-effectiveness plane illustrating scatterplots for rivaroxaban versus enoxaparin and dabigatran versus enoxaparin was produced. Overlap indicates uncertainty that rivaroxaban is more cost-effective than dabigatran. CONCLUSIONS: Basecase analyses indicate that rivaroxaban is more cost-effective than enoxaparin or dabigatran.  PSA indicates that rivaroxaban is the most cost-effective strategy at a €45,000/QALY threshold; however there is uncertainty regarding this strategy being more cost-effective than dabigatran.