Background: Smoking is an important modifiable risk factor for cardiovascular disease, with limited research having been done in Africans. We aimed to determine the association between smoking and measurements of vascular function in Africans and Caucasians. Methods: We determined anthropometric and cardiovascular variables, serum cotinine and C-reactive protein (CRP) in African and Caucasian participants from South Africa (n = 630). Results: Africans had significantly lower body mass index (BMI), higher blood pressure and lower socio-economic status (SES) than Caucasians. Only African smokers showed increased arterial stiffness and a significant correlation between smoking and arterial stiffness. African smokers had increased and Caucasian smokers decreased high-density lipoprotein cholesterol (HDL-C) than the non-smokers. After adjusting for confounders, smoking showed few correlations, mainly with heart rate and CRP. In Africans, smoking also correlated positively with HDL-C, with the opposite result in Caucasians. Conclusion: African smokers had significantly increased arterial stiffness, which was not found in Caucasian smokers. Africans generally demonstrated more associations between smoking and cardiovascular dysfunction than Caucasians. ; CVJA is the official journal of the PASCAR (Pan African Society of Cardiology)