In most risk stratification and intervention postinfarction trials, cardiac mortality is used as the major outcome end point either alone or in combination with nonfatal reinfarction. However, the independent risk carried by nonfatal reinfarction for subsequent cardiac death has not been quantified. The prognostic significance of nonfatal reinfarction was determined from the multicenter diltiazem trial data base of 1,234 patients treated with placebo followed up for 1 to 4 years after acute myocardial infarction. One hundred sixteen patients had at least one nonfatal reinfarction, 14 (12%) of whom subsequently experienced cardiac death. Of the remaining 1,118 patients without nonfatal reinfarction, 110 (9.8%) experienced cardiac death. Compared with event-free patients, patients with nonfatal reinfarction were more likely (p less than 0.05) to be women, to have had an infarction before their index event and to have had prior cardiac-related symptoms. Cox survivorship analyses, using pertinent baseline clinical variables along with nonfatal reinfarction as a time-dependent predictor variable, revealed that nonfatal reinfarction carried a significant and independent risk for subsequent cardiac mortality (hazard ratio 3.0, p = 0.002), which was greater than that carried by other significant predictor variables (New York Heart Association functional class, pulmonary congestion on chest radiograph, blood urea nitrogen level, predischarge Holter-recorded ventricular premature complexes and radionuclide ejection fraction). The cardiac mortality risk associated with nonfatal reinfarction was further increased in patients whose index event was their first infarction (hazard ratio 5.4, p = 0.0006). Thus, nonfatal reinfarction carries a strong, significant and independent risk for subsequent cardiac death in patients surviving an acute myocardial infarction.