Objective Persistent colonisation by Helicobacter pylori, and especially by cagA-positive strains, has been related to several health outcomes with effects in opposite directions. Thus, it is important to evaluate its influence on total and category-specific mortality.

Design We conducted prospective cohort analyses in a nationally representative sample of 9895 participants enrolled in the National Health and Nutrition Examination Survey III to assess the association of H pylori status with all-cause and cause-specific mortality. Analyses for the association of H pylori cagA positivity with mortality were conducted in 7384 subjects with data on H pylori cagA status.

Results In older people (>40.1 years), H pylori was not associated with all-cause mortality (HR 1.00; 95% CI 0.84 to 1.18). There was an inverse association of H pylori status with stroke mortality (HR 0.69; 95% CI 0.44 to 1.08), and the inverse association was stronger for H pylori cagA positivity, with the HR of 0.45 (95% CI 0.27 to 0.76). H pylori was also strongly positively related to gastric cancer mortality. After we adjusted p values using the Benjamini–Hochberg false discovery rate method to account for multiple comparisons, these associations remained, and H pylori status was not related to other outcomes.

Conclusions Our findings suggest that H pylori has a mixed role in human health, but is not a major risk factor for all-cause mortality.