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The prevalence of gastroduodenal lesions is higher in polycythaemia vera (PV) than in the general population. However, the role of Helicobacter pylori (H. pylori) in the pathogenesis of such lesions is unknown. The aim of our study was to evaluate the prevalence of gastroduodenal lesions in PV patients and dyspeptic controls, and to assess the role of PV and H. pylori infection in inducing them. Thirty-five PV patients fulfilling selection criteria and 73 age- and sex-matched controls underwent upper gastrointestinal endoscopy. Six gastric mucosal biopsies were taken in all patients and controls, and analysed for presence of H. pylori; serum anti-CagA was assayed by Western blot. Data were analysed with descriptive statistics and multivariate regression analysis. Compared with controls, PV patients showed a significantly higher frequency of erosions (46% versus 12%), ulcers (29% versus 7%), H. pylori positivity (83% versus 57%), and anti-CagA positivity (66% versus 37%). Fourteen out of 20 (70%) asymptomatic PV patients had gastroduodenal lesions. At multivariate analysis, H. pylori, presence of PV alone, and both PV and anti-CagA were significantly and strongly associated with a higher frequency of gastroduodenal lesions (P < 0.05, P < 0.01 and P < 0.05 respectively). Both PV and H. pylori infection were independent risk factors for gastroduodenal lesions; the underlying pathogenetic mechanism responsible for gastroduodenal lesions in PV possibly involves blood mucosal flow and trophism. The higher susceptibility of H. pylori infection and the high frequency of asymptomatic gastroduodenal lesions in PV patients suggest a surveillance of these patients.