Radioactive iodine (RAI) is considered to be related with hematologic changes. This study aimed to evaluate influence of the first RAI ablation on peripheral complete blood count (CBC) in patients with differentiated thyroid cancer (DTC).Data of CBC at baseline and 6 months after RAI were obtained in 385 patients with DTC with approximately 3700 MBq I (ranging 2220-7585 MBq). Further comparison was done in 196 patients with 1-month postablation data available. Routine blood examinations were performed to determine impact of RAI on white blood cell (WBC), red blood cell (RBC), hemoglobin, platelet, neutrophil, lymphocyte, and monocyte in both sexes. Continuous variables were compared by paired t tests and independent samples t test, and categorical variables were compared by chi-square analysis. Data with repeated measurements were analyzed by analysis of variance.The first RAI after thyroidectomy was associated with mild, yet significant declines in WBC, platelet, and lymphocyte, which persisted for 6 months. One month after RAI, significant declines were found in all CBC, including RBC and hemoglobin (all P < 0.05). While CBC partly recovered 6 months after RAI, this follow-up CBC still demonstrated significant declines in WBC, platelet, and lymphocyte (all P < 0.05) without gender differences. Significant rises in RBC and hemoglobin in males and females were found. The decline of platelet in females was more obvious than in males at 3700 to 4440 MBq of RAI. On the contrary, the rises of RBC and hemoglobin in males were higher than in females. There were no significant complications during the follow-up.WBC and platelet decreased obviously 1 month after RAI. While they partly recovered 6 months after RAI, they were still lower than the baseline. However, RBC and hemoglobin transiently decreased at 1 month and then increased to levels even higher than baseline 6 months later. At 3700 to 4440 MBq of RAI, the decline of platelet in females was more obvious than in males. Yet, rises of RBC and hemoglobin in males were higher than in females. The risks associated with these changes are unlikely to outweigh the potential benefits of RAI in patients with DTC.