The Nifedipine-Total Ischemia Awareness Program was designed to evaluate the prevalence, prognostic implications and effect of therapy on painful and painless myocardial ischemic episodes in a nationwide study of patients with angina pectoris. Three hundred forty-eight patients with at least 2 anginal attacks/week while taking antianginal medications were enrolled at 53 participating centers between September 1, 1986 and March 31, 1988; 312 of the 348 patients formed the study group, while 36 patients formed the control group. At least 1 episode of ST-segment depression during two 48-hour periods of Holter monitoring was present in 136 of the 312 patients in the study group. In these 136 patients, there was a total of 372 episodes of ST-segment depression, of which only 69 (18%) were painful; 85% of the 136 patients had either painless episodes only or both painless and painful episodes. Despite apparently adequate antianginal therapy, 48 patients had ≥3 episodes of ST-segment depression/48 hours of ambulatory electrocardiographic monitoring, and 38 patients >60 minutes of ST-segment depression. After nifedipine was administered, there was a 23% reduction in the mean number of episodes of ST-segment depression (2.7 ± 0.3 to 2.1 ± 0.2, p < 0.01). The most pronounced effects were found in the 48 patients with ≥3 episodes of ST-segment depression and the 38 patients with ≥60 minutes of total ischemic time. In the latter group, the number of episodes was reduced by 45% (5.7 ± 0.9 to 3.2 ±0.6) and the duration of episodes by 47% (127 ±13 to 68 ± 15 minutes, both p < 0.001). Patients taking long-acting nitrates in phase 1 experienced a 46% reduction in the number of episodes when nifedipine was added. Those taking β blockers with or without long-acting nitrates experienced a 20% reduction. In contrast to this reduction in ST-segment depression in the study group (who received nifedipine), there was no change in frequency or duration of ST segment depression in the control group between phase 1 and phase 2.