Objective <p>Using ¹⁸F-FDG PET/CT metabolic parameters to differentiate post-transplant lymphoproliferative disorder (PTLD) and reactive lymphoid hyperplasia (RLH), and PTLD subtypes.</p> Methods <p>¹⁸F-FDG PET/CT and clinical data from 63 PTLD cases and 19 RLH cases were retrospectively collected. According to the 2017 WHO classification, PTLD was categorized into four subtypes: nondestructive (ND-PTLD), polymorphic (P-PTLD), monomorphic (M-PTLD), and classic Hodgkin. Metabolic parameters included maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and at different thresholds of SUVmax (2.5 and 41%), as well as gross tumor volume (GTV) was also collected. Nonparametric test and receiver operating characteristic (ROC) curves were used for statistics.</p> Results <p>There were 42 ND-PTLD patients, 7 P-PTLD patients, and 14&#xa0;M-PTLD patients. Ki-67 was significantly correlated with all metabolic parameters (<i>P</i> all &lt; 0.01). SUVmean, SUVmax, MTV, TLG and GTV were all highest in M-PTLD, followed by P-PTLD, ND-PTLD, and RLH. ROC curves showed ¹⁸F-FDG PET/CT metabolic parameters all had moderate diagnostic efficacy in differentiating between PTLD and RLH, the area under the curves (AUC) range from 0.682 to 0.747. Diagnostic efficacy for P-PTLD + M-PTLD showed excellent performance (AUC for RLH + ND-PTLD vs P-PTLD + M-PTLD was 0.848 for SUVmax, 0.846 for SUVmean_41%, 0.834 for SUVmean_2.5, and 0.819 for GTV). For MTV_41%, TLG _41%, MTV_2.5, TLG_2.5, the AUC was 0.676, 0.761, 0.761, 0.787, respectively.</p> Conclusion <p>¹⁸F-FDG PET/CT metabolic parameters at different thresholds of SUVmax (2.5 and 41%) exhibited comparable diagnostic efficacy for PTLD and its subtypes. All metabolic parameters demonstrated moderate diagnostic efficacy in distinguishing PTLD and RLH. SUVmax, SUVmean_41%, SUVmean_2.5 and GTV showed excellent performance in diagnosing P-PTLD + M-PTLD.</p>