OBJECTIVES There is cross-sectional evidence that CagA antigen produced by Helicobacter pylori is associated with coronary heart disease, stroke, atrial fibrillation (AF) and microalbuminuria, but no large-scale longitudinal studies have been conducted in diabetic patients. We aimed to determine whether cytotoxin-associated gene-A (CagA) seropositivity is independently associated with important vascular outcomes in type 2 diabetes. METHODS We studied 1179 type 2 patients from a well characterized community-based cohort who had available sera from baseline assessment between 1993 and 1996, and follow-up for incident events to end-June 2007. H. pylori IgG and CagA antibodies at baseline were measured by validated ELISA. Multiple logistic/linear regression analysis and Cox proportional hazards modelling were used to determine independent baseline associates of prevalent and incident complications, respectively, including H. pylori/CagA serostatus. RESULTS At baseline, 62.0% of patients were H. pylori seropositive and 37.7% were both H. pylori and CagA seropositive. CagA seropositivity was not independently associated with prevalent coronary heart disease (CHD), cerebrovascular disease (CVD), peripheral arterial disease or AF at baseline (P > 0.41), but there was a significant inverse association with ln(urinary albumin:creatinine) (P = 0.033). There were no independent associations between CagA seropositivity and incident CHD/CVD or progression to microalbuminuria (P > 0.20). During follow-up, 480 patients (40.7%) died, 246 (50.2%) from cardiovascular causes. After adjustment for other variables,CagA seropositivity was weakly protective against cardiovascular death (P = 0.024). CONCLUSION CagA seropositivity is not a risk factor for chronic vascular complications of type 2 diabetes. Assay of CagA antibodies does not contribute significantly to clinical management outside gastroenterological indications.