Increased oxidative stress and vascular inflammation have been shown in patients with cardiac syndrome X (CSX; angina, exercise-induced ischemia, and normal coronary angiogram). This study was conducted to assess the impact of basal superoxide generation by circulating mononuclear cells (MNCs), a contributor to intravascular oxidative stress, and serum inflammatory biomarkers, including high-sensitivity C-reactive protein, homocysteine, soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and von Willebrand factor, on the long-term prognosis of CSX. During a mean follow-up of 31.5 +/- 14.2 months (maximum 5 years), a total of 12 events were recorded in 92 consecutive CSX patients. There were no deaths or myocardial infarctions, but 8 hospitalizations for acute coronary syndrome, 3 for stroke, and 1 for congestive heart failure due to left ventricular systolic dysfunction. Under univariate analysis, only basal superoxide generation by MNCs was associated with the risk for cardiovascular event. Based on multivariate analysis, basal superoxide generation by MNCs could still independently predict future events (relative risk for the highest compared to the lowest tertile, 3.87; 95% confidence interval, 1.42-10.54, p = 0.008). These findings demonstrate that long-term prognosis is fair in patients with CSX. Basal superoxide production of MNCs independently predicts future cardiovascular events, suggesting its potential role in measuring disease progression and risk stratification in these patients.