Aspirin versus enoxaparin for postdischarge venous thromboembolism prophylaxis following orthopedic trauma surgery: An ongoing debate

Background: Accepted venous thromboembolism (VTE) prophylaxis after orthopedic trauma includes anticoagulants and aspirin, with selection varying by patient and injury factors. This study evaluates a single institution’s outcomes after transitioning from low–molecular-weight heparin to aspirin for postdischarge prophylaxis. Methods: This retrospective cohort study of adult patients (≥18 years) with lower extremity or pelvic orthopedic injuries who underwent operative treatment between 2020 and 2024 was identified from the trauma registry of a Level-1 trauma center. Patients were included if they underwent operative fixation during the index hospitalization. Exclusion criteria included a documented VTE or receipt of therapeutic anticoagulation/antiplatelet therapy within six months before admission. The primary outcome was 90-day postdischarge VTE, defined as deep vein thrombosis or pulmonary embolism. Secondary outcomes included 90-day readmission and mortality. Inverse probability of treatment weighting and doubly robust logistic regression were used to compare discharge chemoprophylaxis regimens (aspirin vs. enoxaparin), controlling for age, sex, body mass index, injury severity score, length of stay, comorbidities, and fracture location. Results: A total of 982 patients met inclusion criteria, including 456 (46.4%) patients discharged on aspirin and 526 (53.6%) patients discharged on enoxaparin. Among orthopedic trauma patients, discharge aspirin was associated with significantly higher odds of 90-day postdischarge VTE compared with low–molecular-weight heparin (OR, 4.704; 95% CI, 1.332–16.612; p = 0.016). No significant differences were observed between discharge chemoprophylaxis groups with respect to 90-day readmission or mortality. Conclusions: Low-molecular-weight heparin was associated with lower odds of postdischarge VTE compared with aspirin in this retrospective cohort of orthopedic trauma patients. Further investigation is needed to better define the optimal postdischarge prophylaxis strategy based on individual patient comorbidities and injury patterns. ( J Trauma Acute Care Surg 2026;00:000–000. Copyright © 2026 Wolters Kluwer Health, LLC. All rights reserved.) Level of Evidence: Retrospective, Therapeutic/Care Management; Level 3.