Background: Skin autofluorescence (SAF), as a proxy of AGE accumulation, is predictive of cardiovascular (CVD) complications in i.a. type 2 diabetes mellitus and renal failure, independently of most conventional CVD risk factors. The present exploratory substudy of the Groningen Overweight and Lifestyle (GOAL)-project addresses whether SAF is related to Systematic COronary Risk Evaluation (SCORE) risk estimation (% 10-year CVD-mortality risk) in overweight/obese persons in primary care, without diabetes/renal disease, and if after 3-year treatment of risk factors (change in, Δ) SAF is related to ΔSCORE. Methods: In a sample of 65 participants from the GOAL study, with a body mass index (BMI) >25–40 kg/m 2 , hypertension and/or dyslipidemia, but without diabetes/renal disease, SAF and CVD risk factors were measured at baseline, and after 3 years of lifestyle and pharmaceutical treatment. Results: At baseline, the mean SCORE risk estimation was 3.1±2.6%, mean SAF 2.04±0.5AU. In multivariate analysis SAF was strongly related to age, but not to other risk factors/SCORE. After 3 years ΔSAF was 0.34±0.45 AU (p<0.001). ΔSAF was negatively related to Δbodyweight but not to ΔSCORE%, or its components. At follow-up, SAF was higher in 11 patients with a history of CVD compared to 54 persons without CVD (p=0.002). Conclusions: Baseline and 3-year-Δ SAF are not related to (Δ)SCORE, or its components, except age, in the studied population. ΔSAF was negatively related to Δweight. As 3-year SAF was higher in persons with CVD, these results support a larger study on SAF to assess its contribution to conventional risk factors/SCORE in predicting CVD in overweight persons with low-intermediate cardiovascular risk.