In a randomized, double-blind, placebo-controlled trial, the effects of combined treatment with the antioxidant vitamins A (50,000 IU/day), vitamin C (1,000 mg/day), vitamin E (400 mg/day), and beta-carotene (25 mg/day) were compared for 28 days in 63 (intervention group) and 62 (placebo group) patients with suspected acute myocardial infarction. After treatment with antioxidants, the mean infarct size (creatine kinase and creatine kinase-MB gram equivalents) was significantly less in the antioxidant group than in the placebo group. Serum glutamic-oxaloacetic transaminase decreased by 45.6 IU/dl in the antioxidant group versus 25.8 IU/dl in the placebo group (p < 0.02). Cardiac enzyme lactate dehydrogenase increased slightly (88.6 IU/dl) in the antioxidant group compared with that in the placebo group (166.5 IU/dl) (p < 0.01). QRS score in the electrocardiogram was significantly less in the antioxidant than in the placebo group. The following levels increased in the antioxidant group versus the placebo group, respectively: plasma levels of vitamin E increased by 8.8 and 2.2 mumol/L (p < 0.01), vitamin C increased by 12.6 and 4.2 mumol/L (p < 0.01), beta-carotene increased by 0.28 and 0.06 mumol/L (p < 0.01), and vitamin A increased by 0.36 and 0.12 mumol/L (p < 0.01). Serum lipid peroxides decreased by 1.22 pmol/ml in antioxidant versus 0.22 pmol/ml in the placebo group (p < 0.01). Angina pectoris, total arrhythmias, and poor left ventricular function occurred less often in the antioxidant group. Cardiac end points were significantly less in the antioxidant group (20.6% vs 30.6%, respectively). These results suggest that combined treatment with antioxidant vitamins A, E, C, and beta-carotene in patients with recent acute myocardial infarction may be protective against cardiac necrosis and oxidative stress, and could be beneficial in preventing complications and cardiac event rate in such patients.