Background: Obesity has been related to the incidence of dementia but its impact on cognitive performance in persons without dementia is less clear. We hypothesized that mid-life obesity may modulate the impact of conventional cardiovascular risk factors (CVRF) on cognitive impairment. We tested this hypothesis in the community-based Framingham Offspring Study sample. Methods: At Examination cycle 4 (1988-90) of the Offspring Cohort, indices of obesity (BMI and Waist-Hip Ratio [WHR]) and baseline CVRF levels were ascertained in 1,814 men and women, aged 40-69 years. Obesity and hypertension were related to the score on each of 8 neurocognitive tests measured at Examination 8, 12 years later (1999-2002). Results: Midlife measures of central obesity (WHR in the uppermost quartile- Q4) and of hypertension (BP≥140/≥90 or use of anti-hypertensive medication) were each significantly related to poorer performance on executive function & visuomotor skills (Trails B, Visual Reproductions-Immediate and Delayed Recall). Further, the relation of hypertension to neurocognitive performance was significantly modified by WHR; hypertension was not associated with neurocognitive performance in WHR Q1-Q3, but was associated with a marked adverse performance in Q4 WHR. Neither HTN nor obesity was individually or synergistically related to verbal memory (immediate or delayed recall). Conclusions: Executive function and visuomotor skills were differentially affected by the combined presence of midlife hypertension and Q4 WHR while measures of verbal memory function were not related to these risk factors in our sample, a pattern consistent with vascular cognitive impairment. Control of mid-life elevated blood pressure and central obesity may be strategies to reduce cognitive decline with age.