Background: Preventing pulmonary embolism is a priority after major musculoskeletal surgery. The literature contains discrepant data regarding the influence of anticoagulation on the incidence of pulmonary embolism after joint arthroplasty. The American College of Chest Physicians guidelines recommend administration of oral anticoagulants (warfarin), aiming for an international normalized ratio (INR) level between 2 and 3. However, recent studies show aggressive anticoagulation (INR > 2) can lead to hematoma formation and increased risk of subsequent infection. Questions/purposes: We asked whether an INR greater than 2 protects against pulmonary embolism. Patients and Methods: We identified 9112 patients with 10,122 admissions for joint arthroplasty between 2004 and 2008. All patients received warfarin for prophylaxis, aiming for an INR level of 2 or lower. We assessed 609 of 10,122 admissions (6%) for pulmonary embolism using CT, ventilation/perfusion scan, or pulmonary angiography, and 163 of 10,122 admissions (1.6%) had a proven pulmonary embolism. Results: Fifteen of 163 admissions (9%) had an INR greater than 2 before or on the day of workup compared to 35 of 446 admissions (8%) who were negative. We observed no difference between the INR values in patients with or without pulmonary embolism. Conclusions: We found no clinically relevant difference in the INR values of patients who did or did not develop pulmonary embolism. The risk of bleeding should be weighed against the risk of pulmonary embolism when determining an appropriate target INR for each patient, as an INR less than 2 may reduce the risk of bleeding while still protecting against pulmonary embolism. Level of Evidence: Level III, therapeutic study. See Instructions to Authors for a complete description of levels of evidence.