To examine whether nutritional supplementation of coenzyme Q₁₀ (CoQ₁₀) can reduce myocardial ischemia-reperfusion injury, a group of swine was fed a regular diet supplemented with CoQ₁₀ (5 mg · kg¹ · day¹) for 30 days. Another group of pigs that were fed a regular diet supplemented with placebo served as a control. After 30 days, isolated in situ pig hearts were prepared and hearts were perfused with a cardiopulmonary pump system. Each heart was subjected to 15 min of regional ischemia by snaring of the left anterior descending coronary artery, followed by 60 min of hypothermic cardioplegic global ischemia and 120 min of reperfusion. After the experiments were completed, myocardial infarct size was measured by triphenyltrazolium chloride staining methods. Postischemic left ventricular contractile function was better recovered in the CoQ₁₀ group than in the control group of pigs. CoQ₁₀-fed pigs revealed less myocardial infarction and less creatine kinase release from the coronary effluent compared with control pigs. The experimental group also demonstrated a smaller amount of malonaldehyde in the coronary effluent and a higher content of the endogenous antioxidants ascorbate and thiol. Significant induction of the expression of ubiquitin mRNA was also found in the hearts of the CoQ₁₀-fed group. The results of this study demonstrate that nutritional supplementation of CoQ₁₀ renders the hearts resistant to ischemia-reperfusion injury, probably by reducing the oxidative stress.