OBJECTIVES: Assess cost-effectiveness of 35 days rivaroxaban, an oral direct Factor Xa inhibitor, versus subcutaneous enoxaparin regimens for prevention of venous thromboembolism (VTE) following total hip replacement (THR). METHODS: Rivaroxaban regimens were compared with enoxaparin regimens following THR in two large randomized controlled trials. In RECORD1, patients received 35 days prophylaxis with rivaroxaban or enoxaparin. In RECORD2, patients received 35 days rivaroxaban or 12 days enoxaparin. In RECORD1, rivaroxaban reduced total VTE (composite: any DVT, non-fatal PE, all-cause mortality) by 70% versus enoxaparin after 35 days prophylaxis, although the reduction in symptomatic VTE was not statistically significant. In RECORD2, 35 days rivaroxaban reduced total VTE by 79% and symptomatic VTE by 80% versus 12 days enoxaparin. A cost–utility model (healthcare perspective), populated by the RECORD1-2 trials, assessed cost-effectiveness of rivaroxaban versus both durations of enoxaparin over five years. Risks of VTE and post-thrombotic syndrome beyond the trial period were estimated from published data. Costs, in euros (€), were derived from published Spanish sources. Utilities were derived from published literature. Enoxaparin prophylaxis after THR in Spain lasts approximately 27 days. Hence, in addition to separate analyses based on RECORD1 and 2, RECORD1-2 data were pooled to allow the cost-effectiveness of 35 days rivaroxaban versus the Spanish enoxaparin duration to be estimated. RESULTS: Thirty-five days rivaroxaban dominated 35 days enoxaparin, with a small QALY gain and cost savings of €48.10 per patient.  Rivaroxaban,was also cost-effective versus 12 days enoxaparin (incremental cost per QALY, €3156). Rivaroxaban remained dominant over enoxaparin when RECORD1-2 data were combined (QALY gain, 0.011; cost savings per patient, €12.24). Probabilistic sensitivity analyses showed rivaroxaban dominating in 60% of cases and cost-effective in 100% (cost per QALY; ≤€20,000) CONCLUSIONS: Rivaroxaban is cost-effective versus both 12 days and 35 days enoxaparin, for preventing VTE following THR in Spain.