Context: Data from a large cohort of patients with pulmonary metastases from differentiated thyroid cancer (DTC) were retrospectively analyzed.Objective: To assess the effect of radioiodine therapy and investigate the prognostic factors of survival for patients with pulmonary metastasis secondary to DTC.Methods: A total of 372 patients with pulmonary metastasis from DTC treated with¹³¹I entered the study. According to the results of¹³¹I whole-body scan (WBS), pulmonary metastases were classified as¹³¹I-avid and non-¹³¹I-avid. For patients with¹³¹I-avid lung metastases, treatment response was measured by three parameters: serum thyroglobulin (Tg) levels, chest computed tomography (CT) and post-therapeutic¹³¹I-WBS. Overall survival was calculated by the Kaplan–Meier method. Factors predictive of the outcome were determined by multivariate analyses.Results: Among patients demonstrating¹³¹I-avid pulmonary metastases (256/372, 68.8%), 156 cases (156/256, 60.9%) showed a significant decrease in serum Tg levels after¹³¹I therapy and 138 cases (138/229, 60.3%) showed a reduction in pulmonary metastases on follow-up CT. A complete cure, however, was only achieved in 62 cases (62/256, 24.2%). Multivariate analysis showed that only age, the presence of multiple distant metastases and pulmonary metastatic node size were significant independent variables between the groups of¹³¹I-avid and non-¹³¹I-avid.Conclusion: This study indicated that, most¹³¹I-avid pulmonary metastases from DTC can obtain partial or complete remission after¹³¹I therapy. Younger patients (<40 years old) with only pulmonary metastases and small (‘fine miliaric’ or micronodular) metastases appear to have relative favorite outcomes. Patients who do not respond to¹³¹I treatment have a worse prognosis.