Background: Excess adipose tissue is associated with abnormal lipids, glucose, blood pressure, and inflammatory factors. In children, body mass index percentiles (BMI%) are commonly used to define adiposity. Although waist circumference percentiles (WC%) have not been universally accepted, they may better reflect visceral fat. The objective of this study was to determine the relationship between BMI% and WC% in identifying risk factor patterns in children at risk for developing cardiovascular disease. Methods: Children (8-19y free of major disorders and medications) with obesity, hypertension, lipid disorders, and/or a family history of premature cardiovascular disease (< 55 years in male and <65 years in female first-degree relatives) were recruited from the Preventive Cardiology clinic at Boston Children’s Hospital (n=150). Lifestyle (physical activity, screen time, tobacco exposure), anthropomorphic (height, weight, WC) and blood pressure (SBP, DBP) measures were made, as well as fasting lipids (total cholesterol, HDL, triglycerides (TG), LDL, VLDL) and inflammatory markers (hs-CRP, ICAM-1, P-selectin, and TNFαR2) from a serum sample. Principal component analysis (PCA) with varimax rotation was used to identify independent patterns explaining risk factor variance. Quintiles of pattern scores were associated with BMI% and WC% using multiple linear regression. Results: PCA identified 4 patterns: lipid (low HDL, high TG and LDL), inflammatory (high ICAM and TNFαR2), blood pressure (high SBP and DBP) and Lp(a) [high Lp(a)]. BMI% was significantly associated with higher levels of the lipid and blood pressure patterns (p<0.03), explaining 15.8% and 4.7% of variance (partial r2) respectively. A higher WC% was associated with significantly higher levels of the lipid pattern (p<0.001), explaining 16.2% of variance. When both BMI% and WC% were used together, neither BMI% nor WC% remained associated with the lipid pattern;, however, BMI% was inversely associated (p=0.02) and WC% positively associated (p=0.01) with the inflammatory pattern. The combined use of BMI and WC explained 12.2% of variance in the inflammatory pattern. Conclusion: In a sample of high-risk children, BMI% or WC% explained similar variance in lipid levels; however, the combined use of BMI% (representing lean body mass) and WC% (representing abdominal fat) together explained greater variance in elevated inflammatory factors than either alone. This suggests that using WC% along with BMI% may contribute to cardiovascular risk assessments of high-risk children.