We report results of a case-control study in which we evaluated 41 risk factors potentially associated with the development of post-surgical mediastinitis. There were 163 case patients and 326 control patients. Independent risk factors kept in the final multivariate logistic regression model were obesity (defined as a body mass index of greater than 30), diabetes mellitus, chronic obstructive pulmonary disease, preoperative stay longer than 1 week, pulmonary hypertension, perioperative myocardial infarction, and reoperation.