Patients undergoing orthopedic surgery are at increased risk of venous thromboembolic events. Proven prophylactic measures are available but are generally underused. However, even one of the most effective therapies available, low-molecular-weight heparin, fails to prevent deep vein thrombosis in approximately 15% of patients undergoing total hip replacement. Clinical outcomes and cost-effectiveness of venous thromboembolism prophylaxis may be optimized by tailoring the treatment to the level of risk of each patient. Overall thromboembolic risk depends on the interactions among multiple factors, such as those that relate to the current clinical status and underlying susceptibility of the patient. Presently, risk assessment models that consider these factors may be of practical assistance in stratifying patients. Improving identification of patients with additional risk factors is a goal of future models. Novel therapies, such as the recombinant hirudin desirudin, or strategies, such as prolonged postoperative prophylaxis, may provide improved protection in these patients and should be considered in the future.