Although the number of elderly patients with acute myocardial infarction (AMI) has steadily increased and these patients are known to have a higher early subsequent mortality than younger patients, the reasons for this adverse prognosis are poorly understood. We compared the clinical courses of 217 patients, ages 65 to 75 years, with 631 patients younger than 65 years of age enrolled in the Multicenter Investigation of the Limitation of Infarct Size (MILIS). The older group had a higher prevalence of adverse baseline risk factors, including history of congestive heart failure (14 vs 7%, p less than 0.001), previous AMI (28 vs 22%, p less than 0.05), angina pectoris (42 vs 34%, p less than 0.05), systemic hypertension (64 vs 52%, p less than 0.01), diabetes mellitus (24 vs 17%, p less than 0.05) and female gender (37 vs 24%, p less than 0.001). Despite having a smaller infarct size index than younger patients (15 +/- 1 vs 18 +/- 1 CK-MB g-Eq/m2, p less than 0.002), the elderly patients had a lower admission left ventricular ejection fraction (43 +/- 1 vs 47 +/- 1%, p less than 0.01) and a higher frequency of clinical congestive heart failure (44 vs 28%, p less than 0.001) and in-hospital death (14 vs 7%, p less than 0.01). The 1-year mortality for elderly hospital survivors was also markedly greater (19 vs 5%, p less than 0.001) as was the 4-year mortality (35 vs 13%, p less than 0.001). Adjustment for 7 adverse baseline characteristics in the elderly could account for their increased in-hospital mortality. However, these and 12 additional in-hospital characteristics did not account for the increased 1- and 4-year mortalities of the elderly hospital survivors, which are presumably affected by variables not included in the present age-associated study.