Diltiazem has been reported to reduce the short-term in-hospital reinfarction rate in patients with a non-Q wave myocardial infarction. In the long-term Multicenter Diltiazem Postinfarction Trial, there were 514 patients with non-Q wave myocardial infarction; 279 patients were randomized to the placebo group and 235 to the treatment group. The average follow-up period was 25 months. There was no difference in baseline clinical characteristics between the two groups. Early reinfarction (less-than-or-equal-to 6 months) occurred in 17 patients in the placebo group and in 2 patients in the diltiazem group (p < 0.001). Late reinfarction (>6 months) occurred in 13 patients in the placebo group and in 14 patients in the diltiazem group (p = NS). Initial and reinfarction electrocardiograms (ECGs) were analyzed by using a coding system that permitted identification of standard anatomic areas involved in the infarction process. Thirty-one of the 46 patients had a localized infarction on index and reinfarction ECGs. In the early reinfarction group, 10 (77%) of 13 infarctions occurred in the same ECG region in which the initial infarction had occurred; all 10 were in patients in the placebo group. Among the 18 patients with late reinfarction, the site of the second infarction was the same as that of the first in 9 patients and differed in 9. There was no difference between the placebo and diltiazem groups with respect to location of the infarction. It is concluded that 1) diltiazem reduces the early but not the late rate of reinfarction, 2) early reinfarction tends to occur in the same ECG region as that of the index infarction, and 3) diltiazem may reduce the early reinfarction rate by stabilizing the coronary lesion that caused the index infarction.