BackgroundThis study aimed to explore the timing of pharmacologic prophylaxis initiation after trauma splenectomy and the development of venous thromboembolism (VTE). MethodsRetrospective review of American College of Surgeons Trauma Quality Improvement Program (TQIP) database 2013–2017. Adults (>16 years) with isolated splenic injuries who underwent splenectomy and received pharmacologic VTE prophylaxis were stratified based on timing of initiation of prophylaxis: ≤48 h (EARLY) or > 48 h (LATE) from admission. Patients were matched for demographic and clinical characteristics and outcomes compared. Results3631 patients were included. On logistic regression, LATE prophylaxis was associated with DVT (OR 2.317, p < 0.001) and VTE (OR 2.064, p < 0.001). Low molecular weight heparin (LMWH) was protective for DVT (OR 0.621, p = 0.014) and VTE (OR 0.667, p = 0.015). 1196 patients with EARLY prophylaxis were matched with 1196 patients with LATE prophylaxis. VTE and overall complications were significantly higher in the LATE group (7.4% vs. 4.3%, p = 0.001 and 25.8% vs 16.6%, p < 0.001). ConclusionsLate initiation of VTE prophylaxis is associated with DVT and VTE in post-splenectomy patients, while LMWH is protective.