Patients undergoing total joint arthroplasty are predisposed to the development of venous thromboembolic disease, including deep venous thrombosis and pulmonary embolism. Despite a standard course of postoperative prophylaxis, orthopedic patients remain at significant risk for late venous thromboembolic complications, resulting in considerable morbidity and mortality. Since routine screening for asymptomatic deep venous thrombosis with duplex ultrasound has not been found to be effective, the practice of extended out-of-hospital prophylaxis with low-molecular-weight heparin after total joint arthroplasty has been proposed in order to better protect these patients from delayed venous thromboembolic events. Multiple controlled, randomized clinical trials have shown that extended-duration low-molecular-weight heparin therapy significantly reduces the incidence of asymptomatic venous thromboembolic events following total hip arthroplasty, although no similar benefit has been observed in patients undergoing total knee arthroplasty. There are currently no comparative studies assessing the efficacy of long-term venous thromboembolic prophylaxis with oral anti-coagulant agents. Extending low-molecular-weight heparin therapy is not associated with any increase in major bleeding complications, but it may result in more frequent minor bleeding episodes. In addition, the cost-effectiveness of prolonging low-molecular-weight heparin treatment has not yet been firmly established. Although there is evidence supporting the use of extended out-of-hospital low-molecular-weight heparin prophylaxis after total hip arthroplasty, this strategy has not gained widespread acceptance in North America because of concerns regarding its adverse effects, cost-effectiveness, and uncertain patient compliance. There is general agreement that prophylaxis is needed after hospital discharge, and a minimum of 10 to 14 days of prophylaxis has been shown to be both safe and effective. However, further studies are necessary to determine the optimal duration of treatment.