OBJECTIVES: Assess cost-effectiveness of 35 days rivaroxaban, an oral direct Factor Xa inhibitor, versus 12 days and 35 days subcutaneous enoxaparin for prevention of venous thromboembolism (VTE) following total hip replacement (THR).METHODS: Rivaroxaban regimens were compared with different enoxaparin regimens following THR in two large randomized controlled trials. RECORD1 compared 35 days prophylaxis with rivaroxaban or enoxaparin, while RECORD2 compared 35 days rivaroxaban with 12 days enoxaparin. While the ACCP and NICE recommend up to 35 days prophylaxis in higher-risk patients after THR, a shorter duration is often used in the UK and elsewhere.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 with rivaroxaban was not statistically significant. In RECORD2, rivaroxaban reduced total VTE by 79% and symptomatic VTE by 80% versus 12 days enoxaparin.A cost–utility model (healthcare perspective) assessed cost-effectiveness of rivaroxaban versus both durations of enoxaparin over the five years following surgery. The model was populated by RECORD1-2 data while published epidemiological and clinical data estimated risks of VTE and post-thrombotic syndrome beyond the trial period. Costs (2008 pounds [£]) were derived from published sources. Utilities were taken from a systematic literature review. Potential savings associated with administration and monitoring were also included. RESULTS: Thirty-five days rivaroxaban dominated 35 days enoxaparin, yielding improved health outcomes (QALYs) and savings of £67.82 per patient. Savings were driven mainly by reduced outpatient administration costs. Rivaroxaban also dominated 12 days enoxaparin, with a QALY gain of 0.022 and savings of £22.38. Probabilistic sensitivity analyses showed dominance in 98% of cases versus 35 days enoxaparin and 55% versus 12 days enoxaparin. CONCLUSIONS: Rivaroxaban is cost-effective versus both 12 and 35 days enoxaparin, for prevention of VTE following THR in the UK.