Purpose Epidemiologic studies suggest that insulin-like growth factor-1 (IGF-1) is associated with obesity and, more recently, cancer. This study investigates multiple lifestyle, physiologic, and anthropometric determinants of circulating IGF-1 concentrations. Methods Nationally representative data were used from the cross-sectional Third National Health and Nutrition Examination (NHANES III, 1988–1994) survey, which measured IGF-1 concentrations in blood, from a subsample of participants who were examined in the morning. After exclusion of persons with missing data, 6,058 men and women 20 years of age or older were included in the study. Results The mean IGF-1 concentrations were 260 ng/mL in the entire population and were higher among men as compared with women (278.8 vs. 241.3 ng/mL; p < 0.0001). IGF-1 decreased with increasing age ( p < 0.0001), body mass index ( p < 0.0001), and waist circumference ( p < 0.0001). Individuals with metabolic syndrome had lower IGF-1 concentrations after adjustment for covariates ( p = 0.0008). IGF-1 was inversely associated with increasing number of metabolic syndrome abnormalities ( p = 0.0008). All associations were stronger among women compared with men except across concentrations of glucose. IGF-1 concentrations did not vary by any other lifestyle or physiologic factors. Conclusions Age, adiposity, hyperglycemia, and metabolic syndrome influenced circulating IGF-1 concentrations. Diet and physical activity had no impact on IGF-1 in this nationally representative population.