Objective:The purpose of this study was to investigate the effect and influencing factors of postsurgical radioactive iodine (RAI) therapy for patients with low-and intermediate-risk differentiated thyroid cancer (DTC). Subjects and methods: A retrospective analysis of 423 low-and intermediaterisk DTC patients admitted to the Department of Nuclear Medicine, Sichuan Provincial People's Hospital from January 2005 to December 2020 was performed. All patients were treated with surgery, had a postoperative pathological diagnosis, and were treated with RAI, including 89 males and 334 females. Recurrence risk stratification: 143 cases were low-risk, and 280 cases were intermediaterisk. Results: The excellent response (ER) rate for low-and intermediate-risk were 93.7% and 78.2%, respectively (P < 0.05). There were significant differences in age, cumulative dose of [ 131 I], and pretreatment stimulated-Tg (pre-Tg) levels between the low-and intermediate-risk groups (P < 0.05). There were significant differences in the cumulative dose of 131 I and pre-Tg levels between ER and the non-ER group (P < 0.05). The area under the curve (AUC) values were 0.799 in the low-risk group, and 0.747 in the intermediate-risk group for the ROC curve by ER status of pre-Tg. The ER rate with RAI treatment decreased with an increase in pre-Tg levels. Conclusion: Pre-Tg was an important factor for RAI treatment decision-making and prognostic evaluation and differed between low-risk and intermediate-risk DTC. Aggressive RAI therapy was recommended for low-risk DTC with pre-Tg ≥ 20.0 ng/mL and in intermediate-risk group with pre-Tg ≥ 10.0 ng/mL.