Duodenal ulcer (DU) is a common problem in patients with chronic liver disease (CLD) and with inadequate response to H2 receptor antagonists. Omeprazole might be more effective. In DU-CLD patients, Helicobacter pylori prevalence is low. Nitric oxide is increased in gastric mucosa in cirrhosis. Oxygen-free radicals have a role in gastric inflammation and are abnormal in CLD. Nitrotyrosine is a marker of nitric oxide and oxygen-free radical toxic mucosal reaction. Sixty-nine patients were divided into 2 groups: control (26 patients with DU) and CLD groups (43 patients, DU-CLD). Omeprazole was given (40 mg/day) for 2 or 4 weeks. Symptoms and endoscopy findings were recorded before and after treatment. Antral biopsy specimens were stained for H. pylori and nitrotyrosine. Clinical features of DU are similar in patients with and without CLD. The main presentation was epigastric pain (70%) and bleeding (23%). Healing rate with omeprazole was higher in DU-CLD patients (90.7%) than in controls (80.8%). H. pylori was much lower in DU-CLD patients (51.2%) than controls (96.2%). Nitrotyrosine staining was negative in normal controls (0%) and positive in control-DU (100%), CLD-H. pylori positive (81%), and CLD-H. pylori negative (91%) cases. DU in patients with CLD is not different clinically from those without CLD. Omeprazole effectively and safely treats DU in CLD. Nitric oxide and free oxygen radicals may result in gastric mucosal changes in CLD similar to that caused by H. pylori.