Postoperative deep-vein thrombosis (DVT), venous thromboembolism (VTE), and pulmonary embolism are few of the most serious complications following total joint arthroplasty. Identification of risk factors and initiation of prophylactic measures are the most important measures to prevent the occurrence of DVT. Several protocols and guidelines are published for DVT prophylaxis in TKA, leaving the surgeon still perplexed. Pharmacological and mechanical prophylaxis methods are used to reduce the risk of postoperative symptomatic deep-vein thrombosis and pulmonary embolism. The use of pharmacological methods is based on a fine balance between their efficacy and the adverse effects associated with them. Each of these agents has their own advantages and disadvantages. Several newer agents are getting approved by FDA for the same. Hence, the choice should be carefully made based on the patient characteristics and risk stratification, and the onset of side effects has to be carefully monitored