Background <p>Endoscopic cyanoacrylate injection (ECI) is an established first-line treatment for gastric variceal bleeding (GVB). However, a rare but potentially fatal complication of this therapy is systemic embolization of the cyanoacrylate, most often to the lungs or spleen, while emboli to systemic circulation are exceedingly uncommon.</p> Case presentation <p>We report the case of a 71-year-old Asian male patient with cirrhosis who was found to have gastric variceal bleeding. He underwent endoscopic variceal obliteration using histoacryl (<i>N</i>-butyl cyanoacrylate) injection under intravenous anesthesia. Postprocedure, he exhibited delayed emergence from anesthesia and remained comatose. Laboratory and imaging examinations led to the diagnosis of multiple systemic embolization involving the brain, heart, spleen, and spinal cord, caused by cyanoacrylate.</p> Conclusion <p>Although multiple systemic embolization is extremely rare, clinicians should be vigilant for this complication, especially in patients with abnormal shunts. Careful preprocedural screening for shunts, meticulous injection technique, and close monitoring may facilitate early detection and timely intervention, potentially improving patient outcomes.</p>