Objective: Neutropenia is a complication of Graves' disease (GD) but there is currently no means by which to predict its occurrence. This study aimed to investigate the risk factors for development of neutropenia in untreated GD. Methods: This was a retrospective cohort study. Between January 1, 2010, and July 31, 2020, 1000 patients with new-onset or relapsing GD without treatment were enrolled in the study and divided into two groups: neutropenia group (neutrophil count <2×109/L) and non-neutropenia group (neutrophil count ≥2×109/L). Clinical characteristics of subjects were compared between the two groups and logistic regression analysis applied to determine risk factors for neutropenia. To further explore the correlation of radioactive iodine uptake(RAIU) with neutropenia, subjects were first classified according to quartile of 3hRAIU and 24hRAIU prior to logistic regression analysis. Results: Of all patients recruited, 293 (29.6%) were diagnosed with neutropenia. Compared with non-neutropenic patients, those with neutropenia had a higher level of free thyroxine (FT4) (56.64±31.80 vs. 47.64±39.64, P=0.001), 3hRAIU (55.64±17.04 vs. 49.80±17.21, P<0.001;) and 24hRAIU (67.38±12.54 vs. 64.38±13.58, P<0.001). Univariate logistic regression analysis revealed that FT4、3hRAIU、24hRAIU、creatinine (Cr) and low density lipoprotein (LDL) were risk factors for development of neutropenia in Graves' disease. After adjusting for confounding factors of age, BMI, and sex, we determined that 3hRAIU and 24hRAIU (Model 1: OR=1.021,95%CI 1.008-1.033,P=0.001; Model2: OR=1.023, 95%CI 1.007-1.039,P=0.004), but not FT4, were associated with development of neutropenia. Conclusions: RAIU is associated with neutropenia in patients with untreated Graves' disease.