Background Patients with cyanotic congenital heart disease (C-CHD) usually have myocardial thickening and fibrosis, both of which can affect the course of surgical management. Hypoxia and ischemia may stimulate microvessel formation in the myocardium, which may accelerate the myocardial thickening and fibrosis. Whether hyperplasia of microvessels occurs in the myocardium of C-CHD was investigated in this report. Methods and Results The patients were divided into 2 groups; the C-CHD group (n=22), and the acyanotic congenital heart disease (A-CHD) group (n=24). The microvessels and vascular endothelial growth factor (VEGF) mRNA of the myocardium were detected by inummohistochemical staining assay and real-time quantitative reverse transcriptase polymeric chain reaction, respectively. The serum VEGF levels were measured by using enzyme-linked immunosorbent assay. The results were that: (1) the number of microvessels in the myocardium were more in the C-CHD group than in A-CHD group; (2) the serum VEGF levels in the C-CHD group vs the A-CHD group were higher in the preoperative period (p < 0.001), but there was no difference after operation; and (3) VEGF protein and the expression of VEGF mRNA in the myocardium were higher in the C-CHD group than in the A-CHD group (p < 0.01). Conclusions Myocardial microvessels formed in the myocardium of patients with C-CHD, possibly mediated by increasing VEGF levels (for this group of patients).