The impact of weight change in adulthood on cardiovascular disease is controversial. This study examined the association of change in body weight, from young adulthood to middle age, with average carotid artery intimal-medial wall thickness by B-mode ultrasound measured in middle age. Participants were 13,282 men and women aged 45-64 years from the baseline examination of the Atherosclerosis Risk in Communities (ARIC) Study (1987-1989). Weight change was calculated as the difference between weight at the baseline examination and self-reported weight at age 25. White men gained a mean of 9.7 kg; black men, 10.1 kg; white women, 12.0 kg; and black women, 20.8 kg. Weight change was positively, albeit modestly, associated with intimal-medial thickness in black men and white men and in white women, but not in black women. Adjusted for age, examination center, smoking, education, sports activity level, height, and body mass index at age 25, the differences in intimal-medial thickness associated with a 10-kg increment in weight change were 0.016 (95% confidence interval 0.010 to 0.022) mm in white men, 0.008 (95% confidence interval 0.001 to 0.015) mm in black men, 0.013 (95% confidence interval 0.009 to 0.017) mm in white women, and 0.002 (95% confidence interval -0.002 to 0.006) mm in black women. These findings support the hypothesis that weight gain in adulthood promotes atherosclerotic changes in white men and women and in black men.