Two young man patients with refractory post-bulbar duodenal ulcer (post-bulbar ulcer) were encountered. They had a single punched-out ulcer in the absence of an underlying disease. Patient 1 was Helicobacter pylori (Hp)-positive, and did not respond to Hp eradication therapy. The ulcer scarred after the long-term administration of a proton pump inhibitor (PPI), but recurred after a reduction in the dose. Patient 2 was Hp-negative. His ulcer did not scar even after long-term PPI administration, but it formed a fistula into the gallbladder, and the fistula was surgically closed. In both patients, laboratory and imaging studies excluded Zollinger-Ellison syndrome, but suggested a hyperacidic tendency. Unlike duodenal bulb ulcer (bulbar ulcer), the post-bulbar ulcer in Patient 1 did not heal with Hp eradication therapy, suggesting that post-bulbar ulcer differs etiologically from bulbar ulcer. We speculate that the possible causes of the refractoriness to treatment in both patients were ulcer penetration, callosity formation, and insufficient inhibition of gastric acid secretion due to the impaired passage of PPI into the deep portion of the duodenum as a result of luminal narrowing.