Cognitive impairment may increase the risk of all cardiovascular (CV) events. We prospectively evaluated the independent association between Mini-Mental State Examination (MMSE) score and myocardial infarction, stroke, hospital admission for heart failure and mortality, and their CV composite (major CV events), in a large high-risk CV population. Mini-Mental State Examination was recorded at baseline in 30 959 individuals enrolled into two large parallel trials of patients with prior cardiovascular disease or high-risk diabetes and followed for a median of 56 months. We used a Cox regression model to determine the association between MMSE score and incident CV events and non-CV mortality, adjusted for age, sex, education, history of vascular events, dietary factors, blood pressure, smoking, glucose, low-density lipoprotein, high-density lipoprotein, CV medications, exercise, alcohol intake pattern, depression, and psychosocial stress. Patients were categorized into four groups based on baseline MMSE; 30 (reference), 29-27, 26-24, and <24. Compared with patients with an MMSE of 30 (n = 9624), those with scores of 29-27 [n = 13 867; hazard ratio (HR) 1.08; 95% confidence intervals (CI) 1.01-1.16], 26-24 (n = 4764; HR: 1.15; 95% CI: 1.05-1.26) and <24 (n = 2704; HR: 1.35; 95% CI: 1.21-1.50) had a graded increase in the risk of major vascular events (P < 0.0001). Mini-Mental State Examination score was significantly associated with each of the individual components of the composite, except myocardial infarction. There was also no association between baseline MMSE and hospitalization for unstable or new angina. Within MMSE domains, impairments in orientation to place (HR: 1.52; 1.25-1.85), attention-calculation (HR: 1.10; 1.02-1.18), recall (HR: 1.10; 1.04-1.16), and design copy (HR: 1.15; 1.06-1.24) were the most predictive of major vascular events and mortality. The magnitude of increased risk of CV events associated with an MMSE <24 was similar to a previous history of stroke. In people at increased CV risk, impairments on baseline cognitive testing are associated with a graded increase in the risk of stroke, congestive heart failure, and CV death, but not coronary events. An MMSE score of <24 increased CV disease risk to the same extent as a previous stroke.