Objective: Increased cardiovascular (CV) risk has been reported in adults who are childhood cancer survivors (CCS). We sought to determine the emergence of CV risk factors in CCS while still children. Study design: CCS in remission ≥5 years from cancer diagnosis (n = 319, age = 14.5 years) and their siblings (control subjects, n = 208, age = 13.6 years) participated in this cross-sectional study of CV risk, which included physiologic assessment of insulin sensitivity/resistance (hyperinsulinemic euglycemic clamp). Adjusted comparisons between CCS major diagnoses (leukemia [n = 110], central nervous system tumors [n = 82], solid tumors [n = 127]) and control subjects were performed with linear regression for CV risk factors and insulin sensitivity. Results: Despite no significant differences in weight and body mass index, CCS had greater adiposity (waist [73.1 versus 71.1 cm, P =.02]; percent fat [28.1 versus 25.9%, P =.007]), lower lean body mass (38.4 versus 39.9 kg, P =.01) than control subjects. After adjustment for adiposity, CCS had higher total cholesterol level (154.7 versus148.3 mg/dL, P =.004), low-density lipoprotein cholesterol level (89.4 versus 83.7 mg/dL, P =.002), and triglyceride level (91.8 versus 84 mg/dL, P =.03) and were less insulin sensitive (insulin stimulated glucose uptake, measure of insulin resistance, adjusted for lean body mass 12.1 versus 13.4 mg/kg/min, P =.002) than control subjects. Conclusions: CCS have greater CV risk than healthy children. Because CV risk factors track from childhood to adulthood, early development of altered body composition and decreased insulin sensitivity in CCS may contribute significantly to their risk of early CV morbidity and mortality.