Background <p>Skin autofluorescence (SAF) is a biomarker of tissue accumulation of advanced glycation end-products, which increase the risk of cardiovascular disease (CVD) and mortality, particularly among individuals with chronic kidney disease (CKD) or diabetes mellitus (DM).</p> Objective <p>The aim was to summarise existing evidence and estimate the association between SAF and all-cause mortality, cardiovascular mortality and CVD.</p> Methods <p>A search of Medline, Scopus, Web of Science and the Cochrane Library was conducted from inception to June 2025. Observational studies estimating the association between SAF and all-cause mortality, cardiovascular mortality and CVD were included. Meta-analyses of these associations were performed by categorising SAF (high vs. low) and by 1 arbitrary unit (AU) increment of SAF, expressed as hazard ratio (HR) or odds ratio (OR) and their 95% confidence intervals.</p> Results <p>Thirty-two studies were included in the systematic review. Elevated SAF was associated with an increased risk of all-cause mortality, cardiovascular mortality and CVD. Per 1 AU increase, an HR of 1.51 (1.35, 1.69) was obtained for all-cause mortality, an HR of 1.48 (1.16, 1.90) for cardiovascular mortality and an HR of 1.25 (1.13, 1.38) for CVD. However, estimates with OR tended to be higher. Finally, the results were similar in CKD and DM.</p> Conclusions <p>SAF is a strong predictor of CVD and mortality in general, and in CKD and DM in particular. Integrating SAF measurement into clinical practice could help clinicians implement early and intensive interventions to prevent associated morbidity and mortality, although clinical trials are needed to evaluate its effectiveness.</p> Graphical abstract <p></p>