Background: Epidemiology of peptic ulcer disease (PUD) in India differs from that in the West. It may have undergone a change with recent improvement in hygiene and availability of potent antisecretory and ulcerogenic drugs. We therefore tried to assess time-trends in the frequency of PUD over the past two decades. Methods: Records of patients with uninvestigated dyspepsia and no alarm symptoms who had undergone upper gastrointestinal endoscopy at our institution during the years 1988 (n = 2,358), 1992 (n = 2,240), 1996 (n = 5,261), 2000 (n = 7,051), 2004 (n = 5,767) and 2008 (n = 7,539) were retrospectively reviewed. The frequencies of duodenal and gastric ulcer disease in these groups were compared. Results: Of the 30,216 patients (age:41.7±12.7 years, 34 % females) during the six study periods, 2,360 (7.8 %) had PUD. The frequencies of both duodenal ulcer and gastric ulcer showed a decline from 1988 to 2008, i. e. from 12 % to 2.9 % and 4.5 % to 2.7 %, respectively (p-value <0.001 for trend for each). The decline was more marked for duodenal ulcer, and the ratio of duodenal to gastric ulcer declined from 2.7 in 1988 to 1.1 in 2008. Conclusions: The epidemiology of PUD in India may have changed in the past two decades with the incidence of duodenal ulcer declining more rapidly than that of gastric ulcer. © 2012 Indian Society of Gastroenterology.