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Background: Current treatment regimens that are designed to prevent deep venous thrombosis in patients undergoing orthopaedic procedures rely predominantly on drug prophylaxis alone. The purpose of this randomized clinical study was to evaluate the effectiveness of a mechanical adjunct to chemoprophylaxis that involves intermittent compression of the legs.Methods: During a twenty-two month period, 1803 patients undergoing a variety of orthopaedic procedures were prospectively randomized to receive either chemoprophylaxis alone or a combination of chemoprophylaxis and mechanical prophylaxis. Nine hundred and two patients were managed with low-molecular-weight heparin alone, and 901 were managed with low-molecular-weight heparin and intermittent pneumatic compression of the calves for varying time periods. Twenty-four percent of the patients underwent total hip or knee joint replacement. Screening for deep venous thrombosis was performed on the day of discharge with duplex-color-coded ultrasound.Results: In the chemoprophylaxis-only group, fifteen patients (1.7%) were diagnosed with a deep venous thrombosis; three thromboses were symptomatic. In the chemoprophylaxis plus intermittent pneumatic compression group, four patients (0.4%) were diagnosed with deep venous thrombosis; one thrombosis was symptomatic. The difference between the groups with regard to the prevalence of deep venous thrombosis was significant (p = 0.007). In the chemoprophylaxis plus intermittent pneumatic compression group, no deep venous thromboses were found in patients who received more than six hours of intermittent pneumatic compression daily.Conclusions: Venous thrombosis prophylaxis with low-molecular-weight heparin augmented with a device that delivers rapid-inflation intermittent pneumatic compression to the calves was found to be significantly more effective for preventing deep venous thrombosis when compared with a treatment regimen that involved low-molecular-weight heparin alone.Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.