OBJECTIVE: Description of the clinical, endoscopic, and histopathologic detailed profiles of duodenal affection in portal hypertensive patients. METHODS: A total of 105 patients with chronic liver disease and portal hypertension (PH) were included, upper endoscopy was performed, and two duodenal biopsies were obtained from the bulb and distal to the ampulla, for histopathologic examination. Twenty dyspeptic patients with normal upper endoscopy were included as controls. RESULTS: Of the portal hypertensive patients, 54 (51.4%) had endoscopic duodenopathy (ED) lesions including erythema, erosions, ulcers, telangiectasia, exaggerated villous pattern, duodenal varices, and mixed lesions. ED was significantly higher in patients having severe than mild gastropathy (56.8% vs 23.5%, P < 0.05) with no relation to size of esophageal varices or variceal bleeding. ED was a source of overt bleeding in 6.7% and occult bleeding in 2.9% of patients. Histopathologically, vascular changes included either capillary congestion (in more than half of biopsies) or capillary angiogenesis (in more than one-quarter of biopsies). Nonvascular changes included increased apoptosis (in about 16% of biopsies), fibrous proliferation (in about 4% of biopsies), and villous changes (in 11.4% of distal biopsies). All changes were not statistically different between patients with and without ED. In dyspeptic patients, only minimal histopathologic changes were noted. CONCLUSIONS: ED is significantly higher in patients with severe gastropathy and causes gastrointestinal bleeding in 9.5% of patients. Capillary angiogenesis is an important vascular mechanism for adaptation to PH. The overall existence of histopathologic duodenopathy is much higher than that of ED and occurs with a similar prevalence in patients with and without ED.