Patients with cardiac syndrome X (CSX) have an excellent long-term prognosis, but a significant number show worsening angina over time. Previous studies have found a significant impairment of cardiac uptake of iodine-123-meta-iodobenzylguanidine (MIBG) on myocardial scintigraphy, indicating abnormal function of cardiac adrenergic nerve fibers. The aim of this study was to assess whether cardiac MIBG results can predict symptomatic outcome in patients with CSX. Cardiac MIBG scintigraphy was performed in 40 patients with CSX (mean age 58 ± 5 years, 14 men). Cardiac MIBG uptake was measured by the heart/mediastinum uptake ratio and a single photon-emission computed tomographic regional uptake score (higher values reflected lower uptake). Clinical findings, exercise stress test parameters, sestamibi stress myocardial scintigraphy, and C-reactive protein serum levels were also assessed. At an average follow-up of 79 months (range 36 to 144), no patient had died or developed acute myocardial infarction. Cardiac MIBG defect score was significantly lower in patients with worsening versus those without worsening of angina status (13 ± 7 vs 38 ± 28, p = 0.001), in those with versus those without hospital readmission because of recurrent chest pain (15 ± 9 vs 35 ± 29, p = 0.01), and in those who underwent versus those who did not undergo repeat coronary angiography (11 ± 7 vs 36 ± 27, p = 0.001). Significant correlations were found between quality of life (as assessed by the EuroQoL scale) and heart/mediastinum ratio (r = 0.48, p = 0.002) and cardiac MIBG uptake score (r = -0.69, p <0.001). No other clinical or laboratory variable showed a significant association with clinical end points. In conclusion, in patients with CSX, abnormal function of cardiac adrenergic nerve fibers, as assessed by an impairment of cardiac MIBG uptake, identifies those with worse symptomatic clinical outcomes.