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Notes: Background:  Peptic ulcer disease is mainly caused by Helicobacter pylori infection and the use of non-steroidal anti-inflammatory drugs.Aim:  To investigate the trends in the prevalence of peptic ulcer disease, H. pylori infection and non-steroidal anti-inflammatory drug use in uninvestigated dyspeptic patients over recent years in Hong Kong.Methods:  Data from consecutive patients with uninvestigated dyspeptic symptoms referred by family physicians for open access upper endoscopy during 1997 and 2003 were analysed in relation to peptic ulcer disease, H. pylori infection and non-steroidal anti-inflammatory drug use.Results:  Among 2700 patients included, 405 (15%) had peptic ulcer disease and 14 (0.5%) had gastric cancer. There was a reduced trend from 1997 to 2003 in the prevalence of peptic ulcer disease (17, 20, 14, 16, 13, 14 and 14%, respectively, χ2 = 5.80, P = 0.016) (mainly because of decrease in duodenal ulcers), H. pylori infection (44, 50, 49, 44, 40, 40, 36 and 43%, respectively, χ2 = 13.55, P 〈 0.001) and non-steroidal anti-inflammatory drug use (13, 5, 5, 6, 3, 4, 4 and 5% respectively, χ2 = 13.61, P 〈 0.001). The prevalence of peptic ulcer disease, H. pylori infection and non-steroidal anti-inflammatory drug use between 2001 and 2003 were significantly lower than that between 1997 and 2000 (17% vs. 13%, OR = 0.78, 95% CI: 0.63–0.96, P = 0.020 for peptic ulcer disease; 47% vs. 39%, OR =0.72, 95% CI: 0.60–0.86, P 〈 0.001 for H. pylori infection; and 6% vs. 4%, OR = 0.56, 95% CI: 0.39–0.82, P = 0.002 for non-steroidal anti-inflammatory drug use). H. pylori infection was associated with both duodenal ulcer (OR = 15.87, 95% CI: 10.60–23.76, P 〈 0.001) and gastric ulcer (OR = 3.12, 95% CI: 2.15–4.53, P 〈 0.001) whereas non-steroidal anti-inflammatory drug use was only associated with gastric ulcer (OR = 2.97, 95% CI: 1.70–5.20, P 〈 0.001).Conclusions:  The prevalence of peptic ulcer disease, mainly duodenal ulcers, was reduced in association with a decreasing trend in the prevalence of H. pylori infection and non-steroidal anti-inflammatory drug use from 1997 to 2003.