Background: Papillary thyroid cancer (PTC) is a common endocrine malignancy with relatively good prognosis. Radioactive iodine (RAI) is considered effective for patients with total or nearly total thyroidectomy, but the beneficial effects of RAI are still controversial. Materials and methods: To determine whether RAI therapy could improve the survival rates of PTC patients, we conducted a retrospective analysis using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Disease-specific survival (DSS) was obtained using multivariate Cox proportional hazard regressions. Results: DSS was improved by RAI ablation in patients with tumor >2 cm, age >45 years and gross extrathyroidal or lymph node metastasis. In a further analysis, RAI therapy did not improve the DSS in patients with tumor <2 cm except those with distant metastasis. For patients with tumor >2 cm, those involving gross extrathyroidal extension, age >45 years or disease in the lymph nodes, DSS was improved after RAI therapy. Patients with distant metastasis always benefited from RAI ablation. Conclusion: RAI ablation should be recommended to patients with tumor <2 cm and distant metastasis or patients with tumor >2 cm and one of the following risk factors: gross extrathyroidal extension, age >45 years, lymph node and distant metastases.