Objective: Radioactive iodine (RAI) therapy may cause hematologic abnormalities. The aim of this study is to evaluate long-term hematologic effects in differentiated thyroid cancer (DTC) patients after RAI therapy. Materials and Methods: A total of 1389 patients with DTC who were treated with RAI were retrospectively evaluated. Complete blood cell counts before RAI therapy and at last follow-up and hematologic malignancy development were obtained from the electronic records. Results: In the long-term analysis, thrombocytopenia and lymphopenia were observed significantly in patients over 60 years of age. Thrombocytopenia was observed more frequently in men. Leukopenia, thrombocytopenia, and lymphopenia were observed significantly with doses of >175 mCi. Thrombocytopenia and lymphopenia were observed significantly with multiple dose administration. Higher frequencies of anemia, thrombocytopenia, leukopenia, neutropenia, and lymphopenia were found in patients with advanced-stage disease. However, patients with advanced-stage disease had higher doses and more multiple doses than patients with early-stage disease. The rate of hematologic malignancy was found to be higher than in the general population. Conclusion: We suggest that cytopenia be surveyed more carefully in patients older than 60 years of age. The most important risk factor for lower platelets after RAI therapy is male gender. Clinically, the most important predictor for cytopenia is advanced disease stage, which is related to the combined effects of applied high dose activity, multiple dose applications, and high tumor burden.