Background The basic mechanisms of thromboembolism in cyanotic congenital heart disease (CCHD) have not been well clarified. P-selectin on the platelets reflects platelet activation. Thrombomodulin is a critical cofactor for thrombin-mediated activation of protein C and reflects the anticoagulant activity of the endothelium. The present study was performed to evaluate whether platelet activation exists in patients with CCHD. Methods and Results Platelet P-selectin as a marker of platelet activation, plasma thrombomodulin level and protein C activity as markers of anticoagulant activity of the endothelium and thrombin - antithrombin complex III (TAT) were examined in 35 patients with CCHD. Plasma thrombomodulin level (1.1±0.9 vs 2.2±0.3 FU/ml) and protein C activity (71.1±29.8 vs 117.8±24.8%) were significantly lower in patients with CCHD as compared with the control subjects. The levels of plasma TAT (255±811 vs 1.9±0.9 ng/ml) and P-selectin on platelets (6.3 ±4.5 vs 3.3±0.3 mean fluorescence intensity) were significantly higher in the patients with CCHD than in the controls. Four of the CCHD patients who experienced thromboembolic events had elevated levels of platelet P-selectin (p=0.02) compared with CCHD patients without thromboembolic events. Conclusion Platelet activation exists in patients with CCHD and it may play an important role in the thromboembolic events in CCHD. (Circ J 2007; 71: 948 - 953)