Purpose: The purpose of this study was to evaluate the response of retinoic acid (RA) in radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). Methods: Systematic searches of MEDLINE (from inception to December 2016) and of EMBASE (from inception to December 2016) were performed for English-language publications on thyroid cancer treated with RA. Studies were classified according to the response criteria used: (1) 123I or 131I whole body scintigraphy (WBS), (2) serum thyroglobulin (Tg) level, (3) the response evaluation criteria in solid tumors (RECIST) version 1.0, and (4) World Health Organization (WHO) criteria. Results: Disease response rates as determined by WBS ranged widely between 6.2% and 46.1% with a pooled disease response rate of 27.6% (95% confidence interval: 21.7-34.0%). Response rates as determined by Tg level ranged from 56.6% to 83.3% (pooled response rate 61.3% (51.0-70.9%)), RECIST response rates from 0% to 45.5% (pooled response rate 17.0% (1.4-44.5%)), and according to WHO criteria, the pooled response rate was 30.8% (12.7-52.7%). Conclusions: A minority of patients with RAI-refractory DTC respond to RA treatment.