Background: Periodic ultrasonography (US) examination is recommended in many patients with papillary thyroid carcinoma (PTC) after treatment with radioactive iodine (RAI), but recurrences are confirmed in few cases. This study determined whether the indication of US in the first years after treatment with RAI can be selective when postoperative US and posttherapy whole-body scanning (RxWBS) ruled out persistent neck disease. Methods: This was a prospective study. Two hundred and fifty-four patients with PTC (242 of intermediate risk) undergoing thyroidectomy and RAI, who had no apparent disease at the time of initial therapy (including negative postoperative US and RxWBS), were studied. The patients were followed up for 5 years after treatment with RAI by annual US. Results: At the end of 5 years, 47 patients (18.5%) had at least one suspicious US, but neck recurrence was confirmed in only 4 patients (1.5% of all patients and 8.5% of those with suspicious US). The remaining cases were considered false-positives. US did not reveal disease in the first or second year after treatment with RAI in any patient. In the third, fourth, and fifth year after treatment with RAI, considering only patients with unstimulated Tg < 1 ng/mL in these assessments, US revealed disease in 0, 1 (0.4%), and 1 (0.4%) patient, respectively. Conclusion: The results suggest that low- or intermediate-risk patients with PTC without persistent disease after thyroidectomy (including negative postoperative US and RxWBS) do not require repeat US examination in the first two years after treatment with RAI. In the following years until the fifth year, US can be restricted to patients with Tg ≥1 ng/mL.