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Background. The actual risk of prosthetic joint infection as a result of dental procedures and the role of antibiotic prophylaxis have not been defined. Methods. To examine the association between dental procedures with or without antibiotic prophylaxis and prosthetic hip or knee infection, a prospective, single-center, case-control study for the period 2001-2006 was performed at a 1200-bed tertiary care hospital in Rochester, Minnesota. Case patients were patients hospitalized with total hip or knee infection. Control subjects were patients who underwent a total hip or knee arthroplasty but without a prosthetic joint infection who were hospitalized during the same period on the same orthopedic floor. Data regarding demographic features and potential risk factors were collected. Logistic regression was used to assess the association of variables with the odds of infection. Results. A total of 339 case patients and 339 control subjects were enrolled in the study. There was no increased risk of prosthetic hip or knee infection for patients undergoing a high-risk or low-risk dental procedure who were not administered antibiotic prophylaxis (adjusted odds ratio [OR], 0.8; 95% confidence interval [CI], 0.4-1.6), compared with the risk for patients not undergoing a dental procedure (adjusted OR, 0.6; 95% CI, 0.4-1.1) respectively. Antibiotic prophylaxis in high-risk or low-risk dental procedures did not decrease the risk of subsequent total hip or knee infection (adjusted OR, 0.9 [95% CI, 0.5-1.6] and 1.2 [95% CI, 0.7-2.2], respectively). Conclusions. Dental procedures were not risk factors for subsequent total hip or knee infection. The use of antibiotic prophylaxis prior to dental procedures did not decrease the risk of subsequent total hip or knee infection. [ABSTRACT FROM AUTHOR]