Objective: Venous thromboembolism is associated with substantial morbidity and mortality and is largely preventable. Despite this fact, appropriate prophylaxis is vastly underutilized. To improve compliance with best practice prophylaxis for VTE in hospitalized trauma patients, we implemented a mandatory computerized provider order entry-based clinical decision support tool. The system required completion of checklists of VTE risk factors and contraindications to pharmacologic prophylaxis. With this tool, we were able to determine a patient's risk stratification level and recommend appropriate prophylaxis. To evaluate the effect of our mandatory computerized provider order entry-based clinical decision support tool on compliance with prophylaxis guidelines for venous thromboembolism (VTE) and VTE outcomes among admitted adult trauma patients. Design: Retrospective cohort study (from January 2007 through December 2010). Setting: University-based, state-designated level 1 adult trauma center. Patients: A total of 1599 hospitalized adult trauma patients with a hospital length of stay greater than 1 day. Main Outcome Measures: The primary outcome measure was the proportion of patients whowere ordered riskappropriate guideline-suggestedVTEprophylaxis. The secondary outcome measure was the proportion of patients with any preventable VTE (defined as VTE in a patient not ordered guideline-appropriate VTE prophylaxis), pulmonary embolism, and/or deep vein thrombosis. Results: Compliance with guideline-appropriate prophylaxis increased from 66.2% to 84.4% (P < .001). The rate of preventable harm from VTE decreased from 1.0% to 0.17% (P =.04). Conclusions: Implementation of a mandatory computerized provider order entry-based clinical decision support tool significantly improved compliance with VTE prophylaxis guidelines in hospitalized adult trauma patients. This improved compliance was associated with a significant decrease in the rate of preventable harm, which was defined as VTE events in patients not ordered appropriate prophylaxis.