Background: Multinodular goiter (MNG) is regarded as one of the most common causes of hyperthyroidism, particularly in areas of mild-to-moderate iodine deficiency. The present study aims to explore the effects of the radioactive iodine (RAI) therapy on benign non-toxic MNG and evaluate its side effects. Methods: Patients with benign non-toxic MNG entered the study. Ultrasonography was applied to calculate the percentage of the decrease in the size of the thyroid before and six months minimum after the treatment. Chi-square, Mann-Whiteny-U and T-test were done using SPSS v.18.0 (p<0.05). Results: The volumes of the thyroid lobes and nodules decreased significantly due to RAI therapy (p<0.001). The total volume of the thyroid, volume of the right nodule, and volume of the left nodule decreased by 77.8%, 40.7%, and 34.6% respectively. Conclusion: According to the results of the current study, RAI therapy is an effective treatment method although it has short-term side effects. This treatment option is recommended for patients with benign non-toxic MNG, notably those who cannot be a candidate for surgery. This treatment affects the size of the thyroid and its nodules significantly and decreases almost all of the complications.