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This study aimed to determine clinical association between quantitative hepatic uptake on postablative whole-body scan (WBS) with differentiated thyroid cancer (DTC) prognosis.We analyzed 541 scans of 216 DTC patients who were divided into 3 groups based on radioactive iodine (I-131) WBS uptake and clinical follow-up: group 1 (completion of ablation), group 2 (abnormal uptake in the cervical region), and group 3 (abnormal uptake with distant metastases). For each group, we calculated the ratio of I-131 WBS hepatic uptake (H) to cranial uptake as background (B); this ratio was defined as H/B. Furthermore, we made a distinction between group 1, as having completed radioactive iodine therapy (RIT) (CR), and group 2 and 3, as requiring subsequent RIT (RR).The average H/B scores were 1.34 (median, 1.36; range 1.00–2.1) for group1; 1.89 (median, 1.75; range 1.41–4.20) for group 2; and 2.09 (median, 1.90; range 1.50–4.32) for group 3. Bonferroni multiple comparisons revealed significant differences in H/B among these groups. The H/B of group 1 was significantly smaller than that of other 2 groups (P < 0.0001). The precise cutoff value of H/B for therapeutic effect was ≤1.5. Moreover, 159 of 160 scans in the CR and 375 of 381 patients in the RR were correctly diagnosed using this cutoff value in the final outcome of RIT, yielding a sensitivity, specificity, positive predictive value, and negative predictive value of 99.4%, 98.4%, 99.7%, and 96.3%, respectively.Increased hepatic uptake of I-131 on WBS may predict disease-related progression.