Aims: To assess the cross-sectional associations of the measures of glycemia and cognitive function in subjects at high cardiovascular risk. Methods: Setting and patients: The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and concurrent Telmisartan Randomized Assessment Study in ACE intolerant Subjects with Cardiovascular Disease (TRANSCEND) are multi-center, randomized, controlled investigations of different approaches to angiotensin receptor blockade in over 30,000 high CV risk subjects. Baseline data in both trials was used to analyze relationships between measures of glycemic control and cognition. Outcomes: The univariate and multivariate relationships between diabetes status, fasting plasma glucose (FPG), and scores on the Mini-Mental State Examination (MMSE) were assessed. Results: In subjects with diabetes, the mean MMSE score was 0.4 units lower than in those without diabetes (P < 0.0001). In all subjects, a 1 mmol/L higher FPG value was associated with a MMSE score that was 0.06 units lower (P < 0.0001). The association persisted after adjustment for several cardiovascular risk factors. Conclusions: Dysglycemia is a risk factor for impaired cognitive function in this broadly representative, high-risk study population. Prospective studies can more reliably discern temporal associations, including the effects of glucose lowering in this clinical group.