Background: Despite the efficacy of pharmacotherapy for gastrointestinal ulcers, severe cases of bleeding or perforation due to gastrointestinal ulcers still occur. Giant duodenal ulcer perforation is an uncommon but difficultto- manage pathology with a high mortality rate. We report two cases of giant duodenal ulcer perforation after neurosurgery for brainstem tumors that needed reoperation for gastric disconnection because of postoperative leakage and bleeding. Case presentation: Both cases had undergone neurosurgery for brainstem tumors, and the patients were in a shock state for several days with peritonitis due to giant duodenal perforation. In Case 1, antrectomy with Billroth II reconstruction was performed. However, reoperation for gastric disconnection was needed because of major leakage of gastrojejunostomy and jejunojejunostomy. In Case 2, an omental patch, cholecystectomy, and insertion of a bile drainage tube from the cystic duct were performed for the giant duodenal ulcer, but leakage and bleeding from the ulcer edge required reoperation for gastric disconnection. Conclusions: Brainstem tumors in these cases might have been related to duodenal ulcer perforation with late diagnosis that progressed to severe sepsis. For giant duodenal ulcer perforation with poor general condition, simple closure including omental patch or antrectomy with reconstruction is hazardous. Antrectomy with gastric disconnection, meaning gastrostomy, duodenostomy, feeding jejunostomy and cholecystectomy, is recommended. [ABSTRACT FROM AUTHOR]