Two selective, orally available anticoagulant agents, although with different targets in the coagulation cascade, have recently been approved in many countries on the indication of prophylaxis against venous thromboembolism (VTE) after major joint arthroplasty. This review discusses mainly the antifactor Xa drug, rivaroxaban, with a focus on the orthopedic trials. Pharmacokinetic characteristics and other clinical development programs with rivaroxaban are briefly reviewed. Although the aim of this article is not to review the direct thrombin inhibitor, dabigatran etexilate, some comparisons are made. For clinical results, these are obviously indirect and conclusions must be drawn with caution until head-to-head comparisons are performed. Whether the introduction of rivaroxaban is a change of paradigm will ultimately be decided in the eyes and mind of the beholder.