Approximately 500,000 cases of deep vein thrombosis (DVT) and pulmonary embolism (PE) occur in the United States each year. Of those patients who suffer a massive PE, 70% die within the first hour of symptom onset. Thus, early and aggressive intervention is essential. Clinical evaluation of patients is key in assessing clot risk and is aided by a variety of screening devices, with venography as the gold standard. Patients who undergo hip and knee arthroplasty are at highest risk for DVT and PE. However, appropriate prophylaxis can reduce the incidence significantly. Although standard low-dose heparin is considered to be ineffective, positive experience with the administration of the low-molecular weight heparin (LMWH) enoxaparin, because of the speed of its efficacy in postoperative patients at high risk for DVT, has been reported. The dosage of enoxaparin is weight-adjusted and is sometimes combined with warfarin. Tools for risk-factor assessment and suggested prophylactic regimens for patients undergoing total hip and knee replacement are presented.