ObjectiveRepeat radioiodine (RAI) treatment has been widely implemented for RAI-avid lung metastases and is clinically effective for lung metastatic differentiated thyroid cancer (DTC). We aim to investigate the association between the interval of RAI treatment and short-term response, and the side effects in patients with lung metastases from DTC and to identify predictors for non-effective response to the next RAI treatment.MethodsA total of 282 course pairs from 91 patients were established and categorized into two groups by the interval of neighboring RAI treatment (<12 and ≥12 months), and the characteristics and treatment response between the two groups were compared. Multivariate logistic regression was used to identify predictors associated with treatment response. The side effects in the former course and the latter course were compared while taking into account the interval.ResultsNo significant difference was found between the two groups in treatment response in the latter course (p > 0.05). In the multivariate analysis, age ≥ 55 years (OR = 7.29, 95% CI = 1.66–33.35, p = 0.008), follicular thyroid cancer (OR = 5.00, 95% CI = 1.23–22.18, p = 0.027), and a second RAI treatment as the former course (OR = 4.77, 95% CI = 1.42–18.61, p = 0.016) were significantly associated with a non-effective response. There was no significant difference in the side effects in the former and latter courses between the two groups (p > 0.05).ConclusionThe interval of RAI treatment does not affect short-term response and side effects of DTC patients with RAI-avid lung metastases. It was feasible to defer repeat evaluation and treatment with an interval of at least 12 months to obtain an effective response and reduce the risk of side effects.