Although the extent of enzymatically estimated infarct size appears to be an important determinant of morbidity and mortality early after infarction, its influences on long-term survival and late ventricular dysrhythmia have not yet been characterized. Accordingly, we prospectively studied 173 patients younger than 66 years of age without evidence of prior myocardial infarction, who survived acute myocardial infarction for at least 24 hours. Infarct size was estimated enzymatically and dysrhythmia quantified by computer from two-channel, 24-hour ambulatory ECGs. The mean infarct size index (ISI) of those who died was significantly larger than that of survivors (46.5 ± 5.8 (SEM) vs 21.1 i 1.4 CK-g-Eq/m2, p < 0.001). Overall survival was significantly better after small (ISI < 15 CK-g-Eq/m2) or modest infarcts (15 < ISI < 30) than after large infarcts (ISI 30) (p < 0.01, p < 0.05, respectively). Regardless of the locus of the infarction, patients with small infarcts had a better prognosis than those with larger infarcts. Late mortality was comparable after transmural and subendocardial infarction, but higher after anterior than after inferior infarction (15% vs 6%; p < 0.05). Among the 10 clinical and hemodynamic variables evaluated with multivariate analysis, ISI (but not infarct locus), peak plasma creatine kinase, congestive failure at the time of admission, age and gender were significantly related to mortality. Premature ventricular complexes were more frequent among patients with modest or large infarcts (ISI 15) throughout the follow-up (p < 0.05), regardless of infarct locus. Thus, the extent of infarction is a strong determinant of both ventricular dysrhythmia and mortality, late as well as early after acute myocardial infarction.