Blood-induced arterial segmental spasm has been noticed clinically, and is thought to result from contact between a main feeding artery and extravasating blood from one of its side branches. This localized spasm can persist long enough to compromise the survival of a replantation or flap transfer. A partially amputated rat hind limb model was used to investigate this phenomenon. Bleeding from a side branch was shown to cause severe vasoconstriction and reduced limb perfusion only on direct contact with the main artery. Pretreatment with heparin and minimization of endothelial damage resulted in decreased vasospasm, but aspirin pretreatment had no effect on the degree of spasm and resulting reduced blood flow. This study demonstrates the clinical importance of careful ligation of side branches to reduce vasospasm that may compromise the survival of a replanted part or tissue flap.