BACKGROUND In adults, high blood pressure (BP), adverse serum lipids, and smoking associate with cognitive deficits. The effects of these risk factors from childhood on midlife cognitive performance are unknown. OBJECTIVES This study sought to investigate the associations between childhood/adolescence cardiovascular risk factors and midlife cognitive performance. METHODS From 1980, a population-based cohort of 3,596 children (baseline age: 3 to 18 years) have been followed for 31 years in 3- to 9-year intervals. BP, serum lipids, body mass index, and smoking were assessed in all follow-ups. Cumulative exposure as the area under the curve for each risk factor was determined in childhood (6 to 12 years), adolescence (12 to 18 years), and young adulthood (18 to 24 years). In 2011, cognitive testing was performed in 2,026 participants aged 34 to 49 years. RESULTS High systolic BP, elevated serum total-cholesterol, and smoking from childhood were independently associated with worse midlife cognitive performance, especially memory and learning. The number of early life risk factors, including high levels (extreme 75th percentile for cumulative risk exposure between ages 6 and 24 years) of systolic BP, total-cholesterol, and smoking associated inversely with midlife visual and episodic memory and visuospatial associative learning (-0.140 standard deviations per risk factor, p < 0.0001) and remained significant after adjustment for contemporaneous risk factors. Individuals with all risk factors within recommended levels between ages 6 and 24 years performed 0.29 standard deviations better (p = 0.006) on this cognitive domain than those exceeding all risk factor guidelines at least twice. This difference corresponds to the effect of 6 years aging on this cognitive domain. CONCLUSIONS Cumulative burden of cardiovascular risk factors from childhood/adolescence associate with worse midlife cognitive performance independent of adulthood exposure. (C) 2017 by the American College of Cardiology Foundation.