Objective: Evaluate the efficacy of cumulative doses (CDs) of 131 I-iodide therapy (RIT) in differentiated thyroid cancer (DTC). Subjects and methods: The probability of progressive disease according to CDs was evaluated in patients ≤ 45 years old and > 45 years old and correlated to tumor-node-metastasis (TNM), thyroglobulin values, histological types and variants, age, and zduration of the disease. Results: At the end of a follow-up period of 69 ± 56 months, 85 out of 150 DTC patients submitted to fixed doses RIT had no evidence of disease, 47 had stable disease and 18 had progressive disease. Higher CDs were used in the more aggressive variants (p < 0.0001), higher TNM stages (p < 0.0001), and follicular carcinomas (p = 0.0034). Probability of disease progression was higher with CDs ≥ 600 mCi in patients > 45 years old and with CDs ≥ 800 mCi in patients ≤ 45 years. Conclusion: Although some patients may still respond to high CDs, the impact of further RIT should be carefully evaluated and other treatment strategies may be warranted.