The hypothesis that von Willebrand factor (vWf) release after multiple coronary stenting may be higher than release after single coronary stenting was tested. Preliminary data suggest that multiple stenting is a predictor of thrombosis, and vWf levels in the coronary sinus reflect coronary endothelial injury. Therefore vWf as an indicator of thrombogenesis and endothelial injury was studied. vWf levels were obtained in the coronary sinus at the prestenting and poststenting period in 50 patients with ischemic heart disease who underwent elective coronary stenting (25 patients in single stent group and 25 patients in multiple stent group). Eight subjects who underwent diagnostic coronary angiography were used as controls. vWf levels increased significantly after multiple stenting and vWf levels were significantly different from vWf levels after single stenting. In single stent group, vWf levels in type C lesions were significantly different from levels detected in type A and B lesions. Multiple coronary stenting induces a rapid increase in vWf expression in the coronary circulation. These changes may contribute to the pathogenesis of acute or subacute stent thrombosis and restenosis after multiple stenting.