The aim of this study was to investigate the role of B7-H3 in prognosis of congenital heart disease (CHD) children patients. A total of 65 CHD patients within age 3–12 years who went to our hospital were included during August 2011 to December 2012. Demographic data including age, sex, weight, clinical basic information such as New York Heart Association (NYHA) class, pathological type were collected. Blood samples were collected and serum levels of B7-H3, C-reactive protein (CRP), N-Terminal Pro-Brain Natriuretic Peptide (NT-pro-BNP), and High-sensitivity Troponin T (hsTnT) were determined by enzyme-linked immunosorbent assay (ELISA). Characteristics including age, gender, weight, pathological type, NYHA class, and serum levels of hsTnT and CRP showed no significant difference between deceased and survival patients. However, serum levels of B7-H3 and NT-pro-BNP were significantly higher in deceased patients compared survival patients. Patients with high expressed B7-H3 had higher risks for total major cardiovascular events (MACE) occurrence compared with the lower group. Among the MACE events, significant difference was observed in rates of death, new onset of arrhythmias, and surgical, but not in NYHA class worsening and percutaneous intervention. Patients with higher levels if B7-H3 had significantly higher risk for mortality in the 5-year follow-up compared with the lower group, logic analysis was also conducted and results showed that B7-H3 might be an independent risk factor for 5-year mortality for CHD patients. B7-H3 was up-regulated in dead CHD patients, and serum levels of B7-H3 were related to long-term MACE and 5-year mortality of CHD patients.