Background. The outcome of valvular heart operations in patients with previous mediastinal radiation therapy was studied. Methods. This is a single center retrospective study of 60 patients (37 females, 23 males) with a mean age of 62 ± 15 years (28 to 88 years old) operated on from January 1976 to December 1998. Valvular heart operations performed included aortic valve replacements (n = 26), mitral valve procedures (n = 16), tricuspid valve procedures (n = 6), and multiple valve procedures (n = 12). A total of 264 clinical, hemodynamic, electrocardiographic and echocardiographic variables were analyzed. Results. Total follow-up was 199 patient-years with a mean of 3.3 ± 3.1 years and a range of 0 to 12.4 years old. Early mortality was 7 patients (12%). Early mortality in patients with constrictive pericarditis was 40% (4 of 10) compared with 6% (3 of 50) in patients without constrictive pericarditis. By univariate analysis, early mortality was associated with constrictive pericarditis (p = 0.011), reduced preoperative ejection fraction (p = 0.015), and longer cardiopulmonary bypass times (p = 0.037). A total of 14 patients (23%) required permanent pacemaker placement before (n = 7), during (n = 1), or early (n = 6) after valvular heart operations. There were 19 late deaths (malignancies, 7; heart failures, 5; other cardiac, 4; and other noncardiac, 3). Overall survival and freedom from late cardiac death and cardiac reoperation at 5 years for hospital survivors were 66% ± 8%, 82% ± 7%, and 93% ± 4%, respectively. By univariate analysis, late cardiac death was associated with low ejection fraction (p = 0.002), New York Heart Association (NYHA) functional class IV (p = 0.004), preoperative congestive heart failure (p = 0.02), and preoperative atrial fibrillation (p = 0.038). Eighty-five percent of the discharged patients were in NYHA functional class I or II at follow-up. Conclusions. Early results of valve replacement after mediastinal radiation therapy were good except in the presence of constrictive pericarditis. Long-term outcome was limited by malignancy and heart failure. Early surgical intervention is recommended before the development of risk factors for late death, namely, severe symptoms, left ventricular dysfunction, and atrial fibrillation. © 2001 by The Society of Thoracic Surgeons.