Despite prophylaxis, pulmonary embolism (PE) remains a major cause of posttraumatic morbidity and mortality in high-risk patients. We studied injury-related risk factors associated with the occurrence of PE despite routine prophylaxis. A review of 9721 trauma patients discharged from January 1, 1985 through December 31, 1992, identified 36 patients (0.4%) who suffered clinically evident PE despite a policy of routine prophylaxis against deep venous thrombosis that included use of prophylactic inferior vena caval filters. (Twenty-nine patients had an inferior vena caval filter placed for prophylaxis against PE.) A detailed analysis of injury-related risk factors was performed. Four high-risk patterns of injury were identified, representing common combinations of significant risk factors. These patient groups have an absolute risk of PE despite prophylaxis ranging from 1.5% to 3.8%. The relative risk is approximately ten times that of control patients. Identification of appropriate high-risk groups is necessary to allow optimization of prophylactic measures, including placement of inferior vena caval filter.