The antiischemic properties of nisoldipine, a dihydropyridine calcium antagonist, were assessed in a multicenter, double-blind, placebo-controlled trial by repeated exercise testing and 72-hour ambulatory electrocardiographic monitoring in 82 patients with coronary artery disease. Patients with positive treadmill stress test results and greater than or equal to 2 ischemic episodes per 24 hours were included in this study. Administration of all chronic antiischemic medications except beta blockers were discontinued. During the first week all patients received placebo twice daily. During the second and third weeks, 41 patients received nisoldipine 10 mg and 41 patients received placebo twice daily. In the placebo group there were no changes in exercise parameters or in ambulatory electrocardiographic parameters. In the nisoldipine group, exercise duration increased from 403 to 448 seconds (p = 0.0035), time to 1 mm of ST depression increased from 224 to 298 seconds (p = 0.002), time to pain increased from 241 to 321 seconds (p = 0.01), and maximal ST depression was reduced from 2.6 to 2.3 mm (p = 0.002). Among the ambulatory electrocardiographic parameters in the nisoldipine group, only the number of episodes was reduced, from 14.4 to 11.6 (p = 0.0013) per patient. There was no significant reduction in total ischemic time (132 vs 120 minutes per patient). No significant side effects were observed. This is the largest clinical trial to date on the effects of nisoldipine on myocardial ischemia. The results indicate that nisoldipine was effective in improving all exercise parameters and only partially effective in suppressing ischemia during daily activity.