Venous thromboembolism is a common and potentially lethal disease. Patients who have pulmonary embolism are at especially high risk for death. Death owing to pulmonary embolism is independent of other comorbid conditions (e.g., cancer, chronic heart disease, or lung disease). Sudden death is often the first clinical manifestation. Only a reduction in the incidence of venous thromboembolism can reduce sudden death owing to pulmonary embolism and venous stasis syndrome owing to deep vein thrombosis. The incidence of venous thromboembolism has been relatively constant since about 1980. Improvement in the incidence of venous thromboembolism will require better recognition of persons at risk, improved estimates of the magnitude of risk, the avoidance of risk exposure when possible, more widespread use of safe and effective prophylaxis when risk is unavoidable, and targeting of prophylaxis to those persons who will benefit most. Recognition of venous thromboembolism as a multifactorial disease with genetic and genetic-environmental interaction has provided significant insights into its epidemiology and offers the possibility of improved identification of persons at risk for incident and recurrent venous thromboembolism.