This chapter presents a case scenario of a 70‐year‐old gentleman who presents to orthopedic specialists’ clinic for a preoperative appointment. He is scheduled to undergo a total knee arthroplasty (TKA) for debilitating multicompartmental osteoarthritis. Thromboembolic disease – specifically pulmonary embolism and deep vein thrombosis (DVT) – was once a common and morbid complication following TKA. Ongoing research has endeavored to determine the optimal prophylactic regimen to prevent thromboembolism following TKA. Acetylsalicylic acid may be the more appropriate option in patients at higher risk of bleeding or wound complications. Color doppler‐compression ultrasound has emerged as the most sensitive and specific diagnostic modality to detect DVT, particularly after orthopedic surgery. The duration of required prophylaxis is a common inquiry posed by both patients and orthopedic surgeons. The chapter provides recommendations for implementing evidence‐based practice in the clinical setting.