A 5-mo-old female Rothschild's giraffe (Giraffa camelopardalis rothschildi) presented for regurgitation. Esophagoscopy at 24 wk of age revealed a markedly dilated cranial esophagus with a tight stricture at the level of the heart base consistent with a vascular ring anomaly. Surgical exploration confirmed persistent right fourth aortic arch with ductus originating from left subclavian artery at its junction with the aorta and left subclavian artery. The patent ductus arteriosus was surgically ligated. The procedure was complicated by limited surgical access and vascular friability resulting in uncontrollable hemorrhage, and the animal was euthanatized. The animal's large size and unique shape precluded preoperative examination by computed tomography. Surgical accessibility was poor because cranial retraction of the thoracic limb was limited. Histology revealed focal degeneration of the aorta and subclavian artery and muscular degeneration of the esophagus. Degeneration was attributed to local hypoxia from compression by the vascular structure as the animal grew.