F-18 fluorodeoxyglucose (FDG)-avid metastatic lesions are associated with a poor response to radioiodine ablation therapy (RIT) in papillary thyroid cancer (PTC). This study evaluated the significance of preablative FDG positron emission tomography (PET) for the assessment of risk factors and frequency of malignant FDG-avid lymph nodes in patients with PTC undergoing RIT.The study included 339 consecutive patients (mean age 46.3 ± 12.5 y; 260 females) with PTC referred for the first RIT and who underwent routine preablative FDG PET between April 2011 and February 2013. FDG-avid lymph nodes (FALNs) were identified using retrospective image reviews. The frequency of malignant FALN (mFALN), its contribution to persistent or recurrent PTC, and its risk factors were analyzed.Among the patients, 112 had FALNs (33.0%): 11 mFALNs (3.2%) and 101 benign FALNs (bFALNs, 29.8%). mFALN contributed to 55% of persistent or recurrent PTC after RIT, which was observed in 20 of 339 patients (5.9%) during the post-RIT follow-up. Among preoperative risk factors, suspicious extrathyroidal extension and lateral neck lymph node metastasis on imaging studies were associated with mFALN. Among postoperative risk factors, T3/T4 and N1b stages, higher stimulated thyroglobulin, and higher numbers of metastatic lymph nodes and dissected lymph nodes, were associated with mFALN.mFALNs were observed in a small number of patients with PTC undergoing RIT, but it contributed 55% of total recurrent or persistent disease. Increased frequency of mFALNs is associated with more advanced PTC. Preablative FDG PET has value in evaluation of patients with RIT-resistant lesions and may help determine further treatment strategies.