The objective of this study was to describe longitudinal relations of serum total free fatty acids (FFAs) to insulin resistance (IR) and cardiovascular (CV) risk factors from adolescence into adulthood. The cohort included participants in a longitudinal study of obesity and IR with complete data, including anthropometric measures, FFAs, IR measured by euglycemic clamp, blood pressure, fasting serum lipids, and insulin at mean 15 and 22 years of age (n = 207) and their parents (n = 272). FFAs and IR were not significantly related at mean 15 years of age but were significantly related at mean age 22 years. FFA did not relate to BMI at either age. FFA at 15 years of age estimated IR at 22 years of age. In parents (mean age 51 years), FFA was significantly correlated with BMI, percent body fat, systolic blood pressure, LDL, and IR. Associations with all risk factors except IR in parents were attenuated by adjustment for BMI. Most 22 years of age correlations with parents were higher than corresponding 15 years of age correlations. This study finds that FFA is associated with IR starting in young adulthood. The relation between FFA and CV risk factors does not become significant until later adulthood. The results support a significant impact of early metabolic dysfunction on later CV risk.