BACKGROUND: A diagnostic whole-body scan (WBS) is recommended 6 to 12 months after total thyroidectomy and radioactive iodide ablation in intermediate- or high-risk patients with differentiated thyroid cancer (DTC). The aim of this study was to evaluate the necessity of a diagnostic WBS after radioactive iodide ablation in intermediate-risk patients with DTC. METHODS: A total of 438 subjects were included in the study: 183 low-risk subjects and 255 intermediate-risk subjects according to the American Thyroid Association guideline. All subjects diagnosed with DTC received 1,100 MBq (30 mCi) activity of radioiodine (I-131) following total thyroidectomy. On follow-up, all subjects underwent a diagnostic I-131 WBS after thyroid hormone withdrawal. RESULTS: After initial radioactive iodide ablation, 95.1% of low-risk patients and 91.4% of intermediate-risk patients showed no uptake on diagnostic WBS (P=0.135). Intermediate-risk patients with stimulated thyroglobulin (Tg) levels higher than 2.0 ng/mL showed a greater rate of radioactive iodine uptake on diagnostic WBS. Four intermediate-risk patients showed recurrence during the 16 to 80 months follow-up period. Three of the four patients with recurrence showed no uptake on diagnostic WBS and had a stimulated Tg level less than 2.0 ng/mL. CONCLUSION: A diagnostic I-131 WBS after radioactive iodide ablation in intermediate-risk patients with DTC may not be necessary. A large prospective study is necessary to determine the necessity of diagnostic WBS in intermediate-risk patients with DTC.