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 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. The duration of enoxaparin in RECORD1 represents the ACCP-recommended duration of prophylaxis following THR, but in Canada a shorter duration is often applied.In RECORD1, rivaroxaban reduced total VTE (composite: any DVT, non-fatal PE, all-cause mortality) by 70% versus enoxaparin after 35 days prophylaxis. The reduction in symptomatic VTE with rivaroxaban was not statistically significant and not included in the model. In RECORD2, rivaroxaban reduced total VTE by 79% and symptomatic VTE by 80% versus 12 days enoxaparin.A cost–utility model (Ministry of Health perspective) assessed cost-effectiveness of rivaroxaban versus both durations of enoxaparin over five years. The model is populated by RECORD1-2 trials, while published epidemiological and clinical data estimated the risk of further VTE events and post-thrombotic syndrome beyond the trial period. Costs were derived from published Canadian sources and expressed in 2008 Canadian Dollars (C$). Utilities were derived from published literature. Potential savings from oral administration were also included. RESULTS: Thirty-five days rivaroxaban dominated 35 days enoxaparin, with a small QALY gain and savings of C$282.58 per patient. Cost savings are driven mainly by reduced outpatient administration costs. Probabilistic sensitivity analyses showed this dominance in 98% of cases. Rivaroxaban was also cost-effective versus 12 days enoxaparin, with an incremental cost per QALY of C$33,323. CONCLUSIONS: Rivaroxaban is cost-effective versus both 12 days and 35 days enoxaparin, for the prevention of VTE following THA in Canada.