OBJECTIVES Low serum IGF-I is an independent risk factor for diabetes and cardiovascular disease. These noncommunicable diseases are extremely common in urban black South Africans, but their IGF-I concentration is unknown. We aimed to compare serum IGF-I concentrations of African and Caucasian people, investigate their age-related IGF-I decline, and determine whether IGF-I could account, at least in part, for the high prevalence of noncommunicable diseases in black Africans. RESEARCH DESIGN AND METHODS This cross-sectional study involved 211 African and 316 Caucasian men and women (aged 20-70 yr). Fasting glucose, insulin, lipids, albumin, creatinine, liver enzymes, cotinine, high-sensitivity C-reactive protein, reactive oxygen species, IGF-I, blood pressure (BP), and pulse wave velocity were determined. RESULTS IGF-I was lower in Africans (P < 0.001) and in both ethnicities declined significantly by age quartiles (P < 0.001). In African men and women, IGF-I declined significantly from age quartile 1 to 2 (r = -0.65, P < 0.001), not seen in young Caucasian men and women (r = -0.08, P = 0.45; r = -0.10, P = 0.34). This was confirmed after adjustment for BP, insulin resistance, high-sensitivity C-reactive protein, cotinine, gamma-glutamyl transferase, and reactive oxygen species. Only young Africans showed significant negative correlations of IGF-I with BP, pulse wave velocity, and high-density lipoprotein cholesterol. CONCLUSIONS Africans presented lower IGF-I levels than Caucasians due to an accelerated decline in serum IGF-I concentration prior to 40 yr of age. Strong associations of low serum IGF-I with blood pressure and arterial stiffness in young Africans suggest that the loss of cardiometabolic protection by IGF-I could predispose them to earlier disease onset.