The search for an oral anticoagulant with acceptable efficacy and safety in the treatment and prevention of venous and arterial thromboembolism, but with practical advantages over warfarin, has been a focus of drug development for many years. Three oral agents, dabigatran, rivaroxaban, and apixaban, are nearing approval in the US. Their use in practice will be guided by the clinical trials available, as well as their pharmacokinetic and pharmacodynamic properties. Practitioners need to be fully aware of these characteristics in order to use these agents appropriately in clinical practice. This review compares the results of the phase 3 trials investigating these agents in the prevention of venous thromboembolism in patients undergoing orthopedic surgery, examines the reporting of bleeding complications in the trials, and highlights various practical considerations regarding their use in clinical practice.