The present study aimed to reveal racial differences in the metabolic pattern of C-peptide and non-esterified fatty acids (NEFA), and in their associations with cardiovascular measures in healthy urban African (102) and Caucasian women (115) from South Africa. An oral glucose tolerance test was performed with measurements before and at 30, 60, 90 and 120min. Various cardiovascular parameters and blood lipids were assessed. Statistical analyses were done in a sub-sample of pre-menopausal women. Fasting C-peptide and hepatic insulin extraction were significantly higher in lean African women compared to their Caucasian counterparts, with no racial differences between women with abdominal obesity. Postchallenge C-peptide response and hepatic insulin extraction were significantly higher in Caucasians with abdominal obesity. There were no racial differences in insulin sensitivity and resistance. Despite different associations of C-peptide and NEFA with cardiovascular measures between the ethnicities both showed significant positive correlations with triglycerides. Increased fasting C-peptide levels and unfavorable associations of C-peptide and NEFA with triglycerides and cardiovascular measures implicate a higher cardiovascular risk in lean African women only. This may be of importance for the development of hypertension in this population group.