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The optimal method of prophylaxis for the prevention of pulmonary embolism in patients undergoing total hip arthroplasty remains controversial. Guidelines appear to be contradictory. The purpose of the present study was to examine whether a best prophylactic agent exists for the prevention of postoperative pulmonary embolism and whether the type of anesthesia affects the rates of pulmonary embolism.From 2001 to 2008, a total joint registry from a nationwide health maintenance organization was evaluated to determine the rates of pulmonary embolism, fatal pulmonary embolism, and death among 17,595 patients without a history of venous thromboembolism who were managed with unilateral total hip arthroplasty. All patients were followed for ninety days postoperatively. Data were abstracted electronically and were validated through chart reviews. Multivariate logistic regression models were used to assess associations between the types of prophylaxis and anesthesia that were used and pulmonary embolism while adjusting for other risk factors.Patients received either mechanical prophylaxis alone (N = 1533) or chemical prophylaxis (aspirin [N = 934], Coumadin [warfarin] [N = 6063], or low-molecular-weight heparin [N = 7202]) with or without mechanical prophylaxis. The rate of pulmonary embolism was 0.41% (95% confidence interval [CI], 0.32% to 0.51%) overall, 0.37% (95% CI, 0.05% to 0.70%) for mechanical prophylaxis, 0.43% (95% CI, 0.01% to 0.85%) for aspirin, 0.43% (95% CI, 0.26% to 0.59%) for Coumadin, 0.40% (95% CI, 0.26% to 0.55%) for low-molecular-weight heparin, 0.43% (95% CI, 0.28% to 0.58%) for general anesthesia, and 0.40% (95% CI, 0.28% to 0.52%) for non-general anesthesia. The mortality rate was 0.51% (95% CI, 0.40% to 1.01%) overall, 0.67% (95% CI, 0.23% to 1.34%) for mechanical prophylaxis, 0.64% (95% CI, 0.13% to 1.28%) for aspirin, 0.51% (95% CI, 0.33% to 1.02%) for Coumadin, 0.42% (95% CI, 0.27% to 0.83%) for low-molecular-weight heparin, 0.51% (95% CI, 0.35% to 0.67%) for general anesthesia, and 0.50% (95% CI, 0.36% to 0.64%) for non-general anesthesia. Regression models did not show any association between the type of prophylaxis used or the choice of anesthesia and increased odds of pulmonary embolism when adjusting for age, sex, and American Society of Anesthesiologists score.No clinical differences were detected among the types of prophylaxis against venous thromboembolism or the types of anesthesia with respect to pulmonary embolism, fatal pulmonary embolism, or death on the basis of prospective collection of data by a contemporary total joint registry.Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.