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OBJECTIVE Skin autofluorescence (SAF) has been suggested as a novel and noninvasive technique for assessing tissue accumulation of advanced glycation end products in diabetes and related complications. The aim of this systematic review and meta-analysis was to evaluate the use of SAF in diabetic foot ulcers (DFUs). DATA SOURCES PubMed/MEDLINE and other digital databases. STUDY SELECTION The authors included studies comparing the SAF levels in patients with DFU with a non-DFU group to determine its association with DFU risk. DATA EXTRACTION Collected data included the SAF method and its values in DFU and non-DFU groups, covariates used in adjustment along with the unadjusted and/or multivariate adjusted odds ratios (ORs) for the association of SAF with DFU risk, and other study characteristics. DATA SYNTHESIS A total of six studies were included in this meta-analysis. Five studies that involved 611 participants were included to compare SAF methods. Compared with the non-DFU group, the DFU group showed a significantly increased level of SAF (standardized mean difference, 0.67; 95% confidence interval [CI], 0.32–1.01; P < .001). The results of meta-analysis of ORs revealed that the increased SAF level was independently associated with increased DFU risk in both unadjusted (OR, 3.16; 95% CI, 2.18–4.57; P < .001) and adjusted models (OR, 3.07; 95% CI, 1.95–4.81; P < .001). CONCLUSIONS These findings suggest that SAF could be useful as a novel and noninvasive technology to help determine DFU risk. However, further studies establishing its diagnostic and prognostic utilities are needed.