AbstractAge has been included in various prognostic scoring systems for differentiated thyroid cancer (DTC). The aim of this study is to re-examine the relationship between age and prognosis by using Surveillance, Epidemiology, and End Results (SEER) population-based database. We identified 51,061 DTC patients between 2004 and 2012. Patients were separated into 10-year age groups. Cancer cause-specific survival (CSS) and overall survival (OS) data were obtained. Kaplan-Meier and multivariable Cox models were built to analyze the outcomes and risk factors. Increasing age gradient with a 10-year interval was associated with the trend of higher proportions for male gender, grade III/IV and summary stage of distant metastases. Both CSS and OS continued to worsen with increasing age, being poorest in in the oldest age group (≥71); multivariate analysis confirmed that CSS continued to fall with each age decade, significantly starting at 60 years (HR = 7.5, 95% 1.0–54.1, p = 0.047) compared to the young group (≤20). Similarly, multivariate analysis suggested that OS continued worsening with increasing age, but starting at 40 years (HR = 3.7, 95% 1.4–10.1, p = 0.009) compared to the young group. The current study suggests that an age exceeding 60 years itself represents an unfavorable prognostic factor and high risk for cancer-specific death in DTC.