Childhood obesity predicts adult cardiovascular risk. We hypothesized that the association between childhood body mass index (BMI) and adult carotid intima-media thickness (CIMT) may be modified by levels of adiponectin, an adipocytokine that connects body fatness with cardiovascular risk. The study sample included 1,052 adults (71% white and 29% black, 57% female) aged 23.8 to 43.5 years who were previously examined as children in the Bogalusa Heart Study cohort, with an average follow-up period of 26.5 (range 14.1 to 29.6) years. Childhood BMI, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and systolic blood pressure were standardized to age-specific z-scores. General linear models were used for data analyses. Childhood BMI (p = 0.034), low-density lipoprotein cholesterol (p <0.001), and systolic blood pressure (p = 0.005), along with adult adiponectin levels (p = 0.002) were associated with adult CIMT, adjusted for race, sex, adult age, and cigarette smoking. Further, adult adiponectin levels significantly modified the association between childhood BMI and adult CIMT (P for interaction = 0.0003) such that a significant association between childhood BMI and adult CIMT (p <0.0001) was only observed in those with adiponectin levels below the median. In conclusion, these results suggest that serum adiponectin levels modify the association between childhood obesity and adult atherosclerosis, which has implications for risk stratification and targeted intervention for obese children with low levels of adiponectin.