To analyze the clinical characteristics of differentiated thyroid cancer (DTC) patients with nasolacrimal duct obstruction (NLDO) after Iodine-131 (131I) therapy and provide guidance for clinical decision-making.Thirty-one DTC patients with NLDO were retrospectively enrolled from the Nuclear Medicine Department of Shanxi Bethune Hospital during follow-up of 131I therapy between June 2018 and March 2021. Eight hundred and seventy-one thyroid cancer patients during this period without NLDO after 131I therapy were enrolled as the control group. Clinical characteristics, including sex, age, dose, anti-thyroglobulin antibodies (TGAb), and metastatic lesions, were analyzed by χ2 test and logistic multifactor regression.In the NLDO group and without NLDO group, there were statistically significant differences in gender, age, dose, and whether there was metastasis. Among the NLDO group, the proportion of women, age >55 years old, dose >5.55 GBq, and the presence of metastasis was higher, and the difference was statistically significant; There was no significant difference in the proportion of TGAb positive and negative patients based on 131I therapy (χ2 = 0.27, P = .782).Multivariate logistic regression analysis showed that sex (2.59), age (1.45), dose (2.36), and metastatic lesions (1.93) were all statistically significant influential factors of NLDO after iodine therapy. Significant differences were found in the incidence of NLDO between the number of treatment courses (χ2 = 23.541, P < .001). Prevalence rate of repeat radioiodine therapy (2 times or 3 times and more) is higher than 1 time.Women patients over 55 who had metastatic lesions, and received a dose >5.55 GBq, were more likely to have NLDO. When determining therapeutic doses of 131I, doctors should weigh multiple factors and then give appropriate dosage and suggest that high risk populations be referred for appropriate ophthalmic surgical consultation, for timely diagnosis and therapy.