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As conflicting studies have recently been published, we aimed to determine if Helicobacter pylori (H. pylori) infection is associated with gastric adenocarcinoma.This was a meta-analysis of observational epidemiological studies.A total of 42 studies met the selection criteria and were categorized by the type of study design: eight cohort and 34 case-control studies. The pooled odds ratio for H. pylori in relation to gastric carcinoma was 2.04 (95% CI: 1.69–2.45). Both patient age (OR 0.77, 95% CI: 0.68–0.89) and intestinal type cancers (OR 1.14, 95% CI: 1.05–1.25) were independent effect modifiers. Analysis of other effect modifiers showed no relationship with female gender (OR 0.76, 95% CI: 0.64–0.89), stage of cancer (advanced %) (OR 1.12, 95% CI: 0.88–1.43), anatomical location (cardia %) (OR 1.54, 95% CI: 0.32–7.39) or cohort (nested case-control) studies (OR 1.72, 95% CI: 0.32–9.17). There was significant heterogeneity among the studies (τ2= 149; p < 0.001). The quality of the studies varied considerably, with the majority of excellent studies producing positive results and the very poor to moderate studies producing mixed results.H. pylori infection is associated with a 2-fold increased risk of developing gastric adenocarcinoma.