It is known that xanthine oxidoreductase contributes significantly to ischemia/reperfusion injury by generating reactive oxygen species. Ischemia-modified albumin (IMA) is a biomarker of acute myocardial ischemia with high sensitivity but moderate specificity. Our study aims to evaluate the xanthine oxidase (XO) system and the IMA level in the serum of patients with ischemic heart disease, and their correlation with traditional cardiac markers. The study was conducted on 60 patients with ischemic heart disease and 22 healthy subjects (control group). Subjects were divided into three groups: group I (30 patients with ST-elevated myocardial infarction), group II (30 patients with chronic stable angina), and the control group (22 subjects). The patients and controls had laboratory tests performed including lipid profile, cardiac enzymes, XO, uric acid, and IMA. The serum levels of XO and IMA were significantly higher in group I (1.65 ± 0.29 U/ml and 0.58 ± 0.15 ABSU, respectively) than in group II (1.11 ± 0.20 U/ml and 0.29 ± 0.10 ABSU, respectively) and the control group (0.95 ± 0.16 U/ml and 0.24 ± 0.08 ABSU, respectively) (P < 0.001). There was a significant positive correlation between XO and IMA in group I. Also, there was significant positive correlation between XO or IMA and other cardiac markers, with the highest level of significance between IMA and creatine kinase (CK-MB). In group II only XO activity was significantly elevated in comparison with controls. These results confirm the role of XO enzyme in ischemic heart disease with involvement of IMA, at a detectable level, during the early necrotic phase.