BACKGROUND: Persons with vascular disorders are at higher risk of cognitive decline. OBJECTIVE: To determine whether caffeine may be associated with cognitive decline reduction in elderly at high vascular risk. METHODS: We included 2,475 women aged 65+ years in the Women's Antioxidant Cardiovascular Study, a randomized trial of antioxidants and B vitamins for cardiovascular disease secondary prevention. We ascertained regular caffeine intake at baseline (1995-1996) using a validated 116 item-food frequency questionnaire. From 1998-2000 to 2005-2006, we administered four telephone cognitive assessments at two-year intervals evaluating global cognition, verbal memory, and category fluency. The primary outcome was the change in global cognitive score, which was the average of the z-scores of all tests. We used generalized linear models for repeated measures that were adjusted for various sociodemographic, health, and lifestyle factors to evaluate the difference in cognitive decline rates across quintiles of caffeine intake. RESULTS: We observed significantly slower rates of cognitive decline with increasing caffeine intake (p-trend = 0.02). The rate difference between the highest and lowest quintiles of usual caffeine intake (>371 versus <30 mg/day) was equivalent to that observed between those who were 7 years apart in age (p = 0.006). Consumption of caffeinated coffee was significantly related to slower cognitive decline (p-trend = 0.05), but not other caffeinated products (e.g., decaf, tea, cola, chocolate). We conducted interaction analyses and observed stronger associations in women assigned to vitamin B supplementation (p-interaction = 0.02). CONCLUSIONS: Caffeine intake was related to moderately better cognitive maintenance over 5 years in older women with vascular disorders.