AIM: To assess the clinical characteristics of Helicobacter pylori (H pylori) negative duodenal ulcer. METHODS:Patients with an endoscopic diagnosis of duodenal ulcer between 1996 and 2002 were included in the present study. Patients were considered to be negative for H pylori, if both histological examination and rapid urease test of biopsy specimens were negative. A comparison was made between patients with H pylori positive and negative duodenal ulcers. RESULTS: A total of 1 343 patients were studied. Their mean age was 54.7±0.5 years. There was a male preponderance (M:F=2.5:1). Three hundred and ninety-eight patients (29.6%) did not have H pylori infection. The annual proportion of patients with H pylori negative duodenal ulcers increased progressively from 1996 to 2002. On multivariate analysis, patients with H pylori negative duodenal ulcer were more likely to be older, have concomitant medical problem, pre-existing malignancy, recent surgery, underlying sepsis, or taken non-steroidal anti-inflammatory drugs. In terms of clinical presentations, patients with H pylori negative duodenal ulcer were more likely to present with bleeding, multiple ulcers and larger ulcers. CONCLUSION:The proportion of patients with H pylori negative duodenal ulcers is on the rise because of a continued drop in incidence of H pyloripositive duodenal ulcers in recent years. Such patients have distinct clinical characteristics and it is important to ascertain the H pylori status before starting eradication therapy. METHODS: Patients with an endoscopic diagnosis of duodenal ulcer between 1996 and 2002 were included in the present study. Patients were considered to be negative for H pylori, if Both histological examination and rapid urease test of biopsy specimens were negative. A comparison was made between patients with H pylori positive and negative duodenal ulcers. RESULTS: A total of 1 343 patients were studied. Three hundred and ninety-eight patients (29.6%) did not have H pylori infection. The annual proportion of patients with H pylori negative duodenal ulcers increased progressively from 1996 to 2002. On multivariate analysis, patients with H pylori negative duodenal ulcer were more likely to be older, have concomitant medical problem, pre-existing malignancy, recent surgery, underlying sepsis, or taken non-ste In terms of clinical presentations, patients with H pylori negative duodenal ulcer were more likely to present with bleeding, multiple ulcers and larger ulcers. CONCLUSION: The proportion of patients with H pylori negative duodenal ulcers is on the rise because of a continued drop in incidence of H pyloripositive duodenal ulcers in recent years. Such patients have distinct clinical characteristics and it is important to ascertain the H pylori status before starting eradication therapy.