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Background  Misuse of thromboprophylaxis may increase preventable complications for hospitalized medical patients.    Objectives  To assess the net clinical benefit of a multifaceted intervention in emergency wards (educational lectures, posters, pocket cards, computerized clinical decision support systems and, where feasible, electronic reminders) for the prevention of venous thromboembolism.    Patients/Methods  Prospective cluster-randomized trial in 27 hospitals. After a pre-intervention period, centers were randomized as either intervention (n = 13) or control (n = 14). All patients over 40 years old, admitted to the emergency room, and hospitalized in a medical ward were included, totaling 1,402 (712 intervention and 690 control) and 15,351 (8,359 intervention and 6,992 control) in the pre-intervention and intervention periods, respectively.    Results  Symptomatic venous thromboembolism or major bleeding (primary outcome) occurred at 3 months in 3.1% and 3.2% of patients in the intervention and control groups, respectively (adjusted odds ratio: 1.02 [95% confidence interval: 0.78–1.34]). The rates of thromboembolism (1.9%  vs . 1.9%), major bleedings (1.2%  vs . 1.3%), and mortality (11.3%  vs . 11.1%) did not differ between the groups. Between the pre-intervention and intervention periods, the proportion of patients who received prophylactic anticoagulant treatment more steeply increased in the intervention group (from 35.0% to 48.2%: +13.2%) than the control (40.7% to 44.1%: +3.4%), while the rate of adequate thromboprophylaxis remained stable in both groups (52.4% to 50.9%: -1.5%; 49.1% to 48.8%: -0.3%).    Conclusions  Our intervention neither improved adequate prophylaxis nor reduced the rates of clinical events. New strategies are required to improve thromboembolism prevention for hospitalized medical patients.    Trial Registration  ClinicalTrials.gov  NCT01212393

Multifaceted Intervention to Prevent Venous Thromboembolism in Patients Hospitalized for Acute Medical Illness: A Multicenter Cluster-Randomized Trial