Postoperative mediastinitis complicated 21 (3.4%) of 616 median sternotomy procedures at Beth Israel Hospital (Boston, Mass.) between 1975 and 1979. These cases were analyzed by means of a case control study to identify host and operative risk factors and to characterize the clinical features of mediastinitis. Eighteen patients with mediastinitis (86%) had serious underlying noncardiac diseases, as compared with 14 (33%) of 42 noninfected controls (P = .001). Reoperation was positively associated with infection (P = .03). All patients had abnormal sternal wounds and fever; sternal instability and mediastinal widening were unusual. Twelve patients (57%) were bacteremic. Twenty-four organisms were recovered from the 21 patients with mediastinitis; 13 of the isolates were gram-positive, and 11 were gram-negative. Infections due to gram-negative bacteria appeared earlier and were more likely to be bacteremic (70%). All gram-negative isolates and five of six isolates of Staphylococcus epidermidis were resistant to the antimicrobial agent used perioperatively. Patients were treated with extensive debridement and appropriate antibiotics. The mortality rate was 24% (five of 21). Long-term complications in survivors were not seen.