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Dyspepsia and Helicobacter pylori infection are two important public health issues in the field of gastroenterology, generating high expenditures in diagnosis and treatment. A causal relationship between H. pylori and dyspepsia is still debated. The aim of this study was to address changes in the prevalence of, and association between, dyspepsia and H. pylori infection in a general population. The study took place in the municipality of Sørreisa in Northern Norway. Data were collected in 1987 and 2004. The study included questionnaires on gastrointestinal disorders and risk factors, as well as H. pylori assessment. The prevalence of dyspepsia in 2004 was 31.9% in men and 31.7% in women (compared with 30.7 and 26.3% in 1987). In 2004, the prevalence of H. pylori infection in men with/without dyspepsia was 20.3/26.7% (compared with 47.0/32.7% in 1987), whereas the prevalence of H. pylori infection in women with/without dyspepsia was 31.3/20.8% (compared with 50.0/40.7% in 1987). Since 1987, the prevalence of H. pylori has decreased independently of dyspepsia, most pronounced in the younger age groups, thus indicating a cohort effect. Our findings of a decreasing prevalence of H. pylori, a persistently high prevalence of dyspepsia, and an uneven distribution of H. pylori infection with regard to dyspepsia in men and women, question the understanding of a causal relationship between dyspepsia and H. pylori.