The restoration of antegrade coronary flow soon after myocardial infarction may be beneficial, independent of an effect on left ventricular function. In patients with disease of only the infarct artery, survival is influenced profoundly by the presence or absence of antegrade flow in that artery. This study was done to assess the influence of antegrade coronary perfusion on survival in patients with multivessel coronary artery disease following their first infarction. Over a 10-year period, 110 subjects (70 men and 40 women, aged 30 to 74 years) with infarction and disease of the infarct artery, as well as one or both of the other coronary arteries, were followed on medical therapy for 42 ± 28 months (mean ± SD). Thirty-five patients had partial or complete antegrade perfusion of the infarct artery (group I), whereas the other 75 had no or minimal antegrade perfusion (group II). The groups were similar in age, sex, risk factors for atherosclerotic cardiovascular disease, duration of follow-up, and maintenance medications. In comparison with the group I subjects, those in group II had larger left ventricular volumes, lower ejection fractions, and a markedly increased mortality (6% for group I and 32% for group II, P=0.017). Of the 110 patients, 52 had a left ventricular ejection fraction of 0.50 or less. Of these, the 11 with partial or complete antegrade flow in the infarct artery (group I) were similar to the 41 with no or minimal antegrade flow (group II) in all respects except survival: cardiac mortality was 9% for the group I patients and 49% for the group II subjects (P=0.017). Thus, survival after myocardial infarction is greatly influenced by the presence or absence of antegrade flow in the infarct artery in patients with both single and multivessel coronary artery disease. In subjects with myocardial infarction, the restoration of partial or complete antegrade flow—pharmacologically or mechanically—may be beneficial even if it is accomplished hours to days after the acute event