Patients undergoing total hip and knee arthroplasty are at increased risk for the development of venous thromboembolic disease, and there is general agreement that these patients require prophylaxis. The selection of a prophylactic agent involves a balance between efficacy and safety and often needs to be individualized for specific patients and institutions. Despite extensive research, the ideal agent for prophylaxis against deep venous thrombosis has not been identified. The results of randomized trials indicate that low-molecular-weight heparin, warfarin, and fondaparinux are the most effective prophylactic agents after total hip arthroplasty and that low-molecular-weight heparin, warfarin, fondaparinux, and pneumatic compression boots are the most effective agents after total knee arthroplasty. The duration of prophylaxis against deep venous thrombosis after total hip and knee arthroplasty remains controversial. Prophylaxis should be continued beyond hospital discharge. In the future, the determination of the duration of prophylaxis will be based on the risk stratification of individual patients. The practice of discharging patients from the hospital without prophylaxis, even when the decision is based on negative results of procedures that screen for the presence of deep venous thrombosis, is not cost-effective.