Technical Abstract: BACKGROUND: Cross-sectional data indicate that central adiposity is associated with cardiovascular disease risk, independent of total adiposity. The use of longitudinal data to investigate the relation between changes in fat distribution and the emergence of risk factors is limited. OBJECTIVE: We tested the hypothesis that age-related change in waist circumference (to reflect central adiposity) during adolescence is a significant predictor of longitudinal change in cardiovascular disease risk, after adjustment for change in body mass index (BMI) z score (to reflect total adiposity) in a cohort of postmenarcheal adolescent females. We also tested whether race modified this relation. DESIGN: We analyzed publicly available data from the National Heart, Lung, and Blood Institute Growth and Health Study. Longitudinal regression models were fitted to investigate the independent effects of changes in waist circumference on cardiovascular disease risk factors. RESULTS: Steeper age-related increases in waist circumference over time were associated with a greater increase in LDL-cholesterol concentrations, systolic blood pressure, diastolic blood pressure, and homeostasis model assessment of insulin resistance, after adjustment for BMI z score, in white but not in black females. Change in waist circumference was not a statistically significant predictor of age-related changes in HDL-cholesterol, triglyceride, insulin, and glucose concentrations, after adjustment for changes in BMI z score, in either white or black females. CONCLUSIONS: Our research suggests that monitoring waist circumference in addition to BMI z score has the potential to identify adolescents at risk of the emergence of cardiovascular disease risk factors, at least in white females. The data also suggest that race may modify the relation between fat distribution pattern and cardiovascular disease risk factors.