Pulmonary embolism (PE) and deep vein thrombosis (DVT) are collectively known as venous thromboembolism (VTE). VTE affects an estimated 900,000 Americans every year, resulting in significant morbidity and mortality. Although the average annual incidence of DVT currently ranges from 48 to 122 per 100,000 in the United States, rates will rise with the aging population. There are significant adverse consequences of DVT and PE, including an estimated 300,000 fatalities annually and hundreds of thousands of hospitalizations in nonfatal cases. In addition, a diagnosis of DVT or of PE in the hospital increases the costs of the hospitalization by roughly $10,000 and $20,000, respectively. Thus, VTE is an important patient safety issue with significant morbidity, mortality, and health care costs. Accordingly, the comparative effectiveness and safety of interventions for the prevention and treatment of VTE are among the national priorities for comparative effectiveness research. In this review, we describe the evidence about prevention of DVT in "special populations." Special populations are those patients for whom the benefit and risk of VTE prophylaxis are uncertain, or patients for whom there is decisional uncertainty about the optimal choice, timing, and dose of VTE prophylaxis, or significant practice variation. The burden of VTE is higher among some patient populations, including patients who have experienced recent trauma, traumatic brain injury or burns; patients undergoing bariatric surgery; and patients with acute renal failure, chronic renal failure, or end-stage renal disease. Some of these patient groups have a high risk of bleeding, the most important complication of VTE prophylaxis. Therefore, the risk-benefit ratio of prophylactic medications in these populations is uncertain and is similarly unclear for patients with altered clearance of medications. This report includes our review of the evidence on the efficacy, effectiveness, and safety of pharmacological and mechanical methods of prophylaxis in our defined special populations. The Key Questions (KQs) we explored are as follows: KQ 1. What are the comparative effectiveness and safety of IVC filters to prevent PE in hospitalized patients with trauma? KQ 2a. What are the comparative effectiveness and safety of pharmacologic and mechanical strategies to prevent VTE in hospitalized patients with traumatic brain injury? KQ 2b. What is the optimal timing of initiation and duration of pharmacologic prophylaxis to prevent VTE in hospitalized patients with traumatic brain injury? KQ 3. What are the comparative effectiveness and safety of pharmacologic and mechanical strategies to prevent VTE in hospitalized patients with burns? KQ 4. What are the comparative effectiveness and safety of pharmacologic and mechanical strategies to prevent VTE in hospitalized patients with liver disease? KQ 5. What are the comparative effectiveness and safety of pharmacologic and mechanical strategies to prevent VTE in hospitalized patients receiving antiplatelet therapy? KQ 6. What are the comparative effectiveness and safety of pharmacologic and mechanical strategies to prevent VTE in patients having bariatric surgery? KQ 7. What are the comparative effectiveness and safety of pharmacologic prophylaxis for prevention of VTE during hospitalization of obese and underweight patients? KQ 8. What are the comparative effectiveness and safety of pharmacologic prophylaxis for prevention of VTE during hospitalization of patients with acute kidney injury, moderate renal impairment, or severe renal impairment not undergoing dialysis and patients receiving dialysis?