A 62-year-old Caucasian man with past medical history significant for coronary artery disease, status post drug eluting stent to the left anterior descending artery 10 years prior, was admitted for elective total right knee arthroplasty. His intraoperative course was uneventful, and he was discharged on hospital day 2 on aspirin 325 mg twice daily for 6 weeks for venous thromboembolism (VTE) prophylaxis. Three weeks later the patient developed chest pain shortly after an approximately 1-hour flight and presented to a local emergency department where computed tomography angiogram showed pulmonary emboli involving segmental and subsegmental pulmonary arteries bilaterally. He was transitioned from aspirin 325 mg twice a day to rivaroxaban 15 mg twice daily for 21 days, with a plan to transition to 20 mg daily to complete a 3-month course. He returned to his primary care physician 6 days after discharge with questions about his current anticoagulation therapy as well as the regimen he was on prior to the pulmonary embolism. Two major organizations, The American Academy of Orthopedic Surgeons and The American College of Chest Physicians, provide recommendations for VTE prophylaxis, but they differ regarding the preferred pharmacologic modality and duration. Although the goal is to provide optimal patient care, lack of guideline consensus may lead to different postoperative recommendations. It is important for clinicians to discuss with their patients the pharmacologic options available for VTE prophylaxis, how organizations differ in their recommendations, and the limitations of these pharmacologic agents.