BACKGROUND: The relationship between Helicobacter pylori infection and pancreatic cancer has been investigated in three previous studies with contradictory results. The aim of the present study was to investigate the association between H. pylori seropositivity and the risk for pancreatic cancer in a nested case-control study within a population based cohort. METHODS: Selected birth-year cohorts (born 1921-1949) of residents in Malmö, Sweden, were invited to a health screening investigation. A total of 33 346 subjects participated. Cases with pancreatic cancer (n = 87) were matched to controls (n = 263) using age, sex and time for baseline investigation as matching variables. H. pylori serology was analysed in stored serum samples using an enzyme-linked immunosorbent assay. Odds ratios (OR) for pancreatic cancer were calculated with 95% confidence intervals (CI) using logistic regression. RESULTS: H. pylori seropositivity was not associated with pancreatic cancer in the total cohort (adjusted OR 1.25 (0.75-2.09)). However, a statistically significant association was found in never smokers (OR 3.81 (1.06-13.63) adjusted for alcohol consumption) and a borderline statistically significant association was found in subjects with low alcohol consumption (OR 2.13 (0.97-4.69) adjusted for smoking). CONCLUSION: We conclude that no association between H. pylori infection and the risk for pancreatic cancer was found in the total cohort. However, in never smokers and in subjects with low risk alcohol consumption, a positive H. pylori serology was associated with an increased risk for pancreatic cancer. These findings should be interpreted cautiously due to the limited number of cases in these subgroups.