Diagnosing fracture-related infection (FRI) without clinical confirmatory signs is challenging. [18F]FDG-PET/CT has been shown to have good diagnostic accuracy. However, direct interpretation criteria are lacking. The aim of this study was to assess the diagnostic value of increased FDG-uptake in locoregional lymph nodes on [18F]FDG-PET/CT in patients with suspected upper and lower extremity FRI. : This was a retrospective cohort study of patients who underwent [18F]FDG-PET/CT for suspected extremity FRI in two tertiary referral centers between January 2011 and December 2023. The sensitivity, specificity and diagnostic value of the presence, number and intensity of [18F]FDG uptake in locoregional lymph nodes was assessed. Uptake intensity was measured by calculating the maximum standard uptake value (SUVmax) of the 'hottest' lymph node. All scans were acquired according to the European Association of Nuclear Medicine (EANM) standards, and quantification was performed based on standardized EARL reconstructed images. FRI was diagnosed based on positive intra-operative microbiology results or development of clinical confirmatory signs within six months of follow-up. : One-hundred-and-twenty-four patients were included in the analysis, with 71 cases of confirmed FRI. The presence of locoregional lymph nodes alone showed poor diagnostic accuracy (sensitivity 55%, specificity 68%, diagnostic accuracy 62%). The number of active lymph nodes showed poor discriminative performance between FRI and non-infectious cases (AUC 0.63). Utilizing the SUVmax of the 'hottest' lymph nodes showed a moderate discriminative performance with an AUC of 0.71. The optimal cutoff point (SUVmax 3.48) resulted in a sensitivity of 72%, a specificity of 78% and a diagnostic accuracy of 75%. A logistic regression model was fitted to calculate the added value of lymph node assessment to the regular [18F]FDG-PET/CT assessment. This resulted in a sensitivity of 71%, a specificity of 82% and a diagnostic accuracy of 76%. : Presence and number of locoregional lymph nodes with increased [18F]FDG-uptake alone has poor diagnostic accuracy for FRI. The SUVmax of the 'hottest' lymph node showed moderate diagnostic performance. Lymph node assessment slightly increased the diagnostic value of regular [18F]FDG-PET/CT assessment. Based on these results, increased [18F]FDG-uptake in locoregional lymph nodes should only be considered as a suggestive sign for a positive scan result in suspected FRI.