Previously reported cases of iatrogenic sphenopalatine artery (SPA) pseudoaneurysm have occurred only after trans-sphenoidal surgery for pituitary tumors or maxillofacial surgery. In this article, the author presents what to the best of her knowledge is the first reported case of an SPA pseudoaneurysm that developed following endoscopic sinus surgery (ESS). The patient was a 76-year-old woman with myelodysplastic syndrome who presented with a 6-month history of unilateral sinus symptoms. She underwent septoplasty and unilateral ESS, which included frontal recess clearance and sphenoidotomy. However, during surgery, severe generalized bleeding was encountered. The bleeding was arrested only after anterior and posterior nasal packing. After two attempts to remove the packing failed, angiography was obtained. It revealed an SPA pseudoaneurysm, which was immediately and successfully embolized. SPA pseudoaneurysm is a rare but significant complication of ESS, and it should be considered in patients with posterior epistaxis after ESS or prolonged posterior nasal packing. The pathogenesis may include intraoperative trauma, infection, pressure necrosis from packing, or a combination of these factors. Optimal management includes either ligation or embolization, depending on anatomic, patient, staff, and resource factors. The author reviews the pertinent anatomy and the pathophysiology, diagnosis, management, and prevention of this rare complication.