This research paper summarizes the results of the cost-effectiveness study of apixaban vs enoxaparin, in the prevention of venous thromboembolism, after knee and hip orthopedic surgery. The cost-effectiveness analysis, performed assuming the National Health System perspective, and considering a time horizon of three months, adopted an analytical decision model in the form of a decision three. The data associated with clinical effectiveness was retrieved from prospective, controlled clinical trials, that compared head-to-head apixaban and enovaparin. Clinical practice and resource use were derived from literature, and validated with an clinical expert. The unit cost associated to the health resources was based in official data sources from the Portuguese Health Ministry (Portaria nº 839-A/2009, de 31 de julho; INFARMED; and ACSS). For knee replacement therapy, apixaban was the dominant option, when compared to enoxaparin. Apixaban was a dominant alternative when compared with Enoxaparin for both types of orthopedic surgery.