This study was conducted to compare the staging systems for the prediction of long-term disease status in patients with well-differentiated thyroid carcinoma (WDTC), and to find out the earliest postoperative period predictor of long-term persistence/recurrence of disease. Patients with WDTC (n = 356; Mage = 41.5 ± 12.7 years) followed for at least five years (12.3 ± 5.0 years) after thyroidectomy and 131I remnant ablation at a tertiary regional hospital in Taiwan were retrospectively studied. Each patient was risk stratified using the American Joint Cancer Committee (stage I-IV) and American Thyroid Association (low, intermediate, and high risk) staging systems after operation and first 131I remnant ablation and using response to initial therapy reclassification (RTR; excellent, indeterminate, biochemical incomplete, and structural incomplete response) system, which is determined 6-24 months after the first 131I ablation. The clinical outcome was defined as no evidence of disease (NED; suppressed thyroglobulin [Tg] <0.5 ng/mL, stimulated Tg <1 ng/mL, and no structural detectable disease), biochemical persistent disease (BPD; suppressed Tg ≥0.5 ng/mL or stimulated Tg ≥1 ng/mL in the absence of structural disease), structural persistent disease (SPD; locoregional or distant metastases with any Tg level), or recurrent disease (RD; biochemical or structural disease identified after a period of NED). At the time of final follow-up, 78.4% (n = 279) of the patients had NED, 9.3% (n = 33) had BPD, 10.1% (n = 36) had SPD, and 2.2% (n = 8) developed RD. All three systems could predict the increasing trend of SPD and the decreasing trend of NED with advancing stage of disease. However, the ATA risk estimates could be significantly refined by the RTR system, especially for the ATA high-risk group, in which 29.2% developed SPD/RD during follow-up. The RTR system reduced the likelihood of finding SPD/RD to 3.7% in those demonstrating an excellent response to therapy, and increased the likelihood to 78.6% in those demonstrating a structural incomplete response. Among the earliest postoperative factors, only the Tg level at the first 131I ablation could predict long-term persistence/recurrence. The results highly support incorporating the RTR system to modify the initial risk estimate during follow-up among Chinese patients with WDTC.