Venous thromboembolic disease (VTED) is a major cause of morbidity and mortality after total knee arthroplasty (TKA). Current VTED prophylaxis protocols consist of early mobilization, mechanical compression devices, and pharmacologic agents. Venous phasic flow-regulated below-knee devices are generally favored, but the optimal duration and method of mechanical prophylaxis is unknown. Risk stratification models have been developed to guide pharmacologic prophylaxis. For patients with standard VTED risk profile, aspirin has become increasingly popular. Recent studies have validated the efficacy, relatively low bleeding risks, and cost-effectiveness of aspirin in the patients with standard risk profile. Current evidence suggests that the newer oral anticoagulants, including the factor Xa and the direct thrombin inhibitors, are effective for the reduction of postoperative VTED but may be associated with increased bleeding and wound complication rates.