We report the results of a case-control study of postsurgical mediastinitis (PSM) that we conducted from 1985 to 1993. The incidence of PSM was 2.2% (81 of 3,711 cases who underwent sternotomy); we analyzed the findings for 73 cases and 73 controls. Univariate analysis revealed that the risk factors for PSM were emergency surgery (27% of cases vs. 13% of controls), New York Heart Association functional class IV (46.5% vs. 21.9%), heart transplantation (12% vs. 0), and coronary artery bypass graft (CABG) surgery (60% vs. 41%). The incidences of fever, reoperation for bleeding, pacemaker placement, use of vasoactive drugs, prolonged mechanical ventilation, use of central lines, and treatment in the intensive care unit were also higher for cases. Multivariate analysis identified the following independent risk factors for PSM: reoperation (risk ratio [RR], 9.2), need for vasoactive drugs (RR, 3.5), CABG surgery (RR, 3.2), and fever that persisted after the third postsurgical day (RR, 406). The related mortality was 13.7%, and death was significantly more frequent among cases (17.7%) than among controls (2.7%). Multivariate analysis identified the following independent risk factors for mortality: bacteremia (RR, 21.5), the use of an intraaortic balloon (RR, 14.9), advanced age (RR, 1.14 per year), and prolonged mechanical ventilation (RR, 1.1 per day).