Objective: To assess the efficacy and safety of low- (1 100 mBq) and high-dose (3 700 mBq) iodine-131 (131I) for postoperative ablation of thyroid remnant in patients with differentiated thyroid cancer by using Meta-analysis. Methods: The literature of randomized clinical trials (RCT) concerning low- versus high-dose 131I in postoperative ablation of thyroid remnant in patients with differentiated thyroid cancer was searched using the national and international electronic databases. All relevant studies were screened according to inclusion and exclusion criteria, and then the included studies were evaluated, and finally, the extracted data were analyzed using RevMan 5.0 software provided by the Cochrane Collaboration. Results: Six RCTs were included, with a total of 1 141 patients (715 patients in low dose 131I group and 696 patients in high-dose 131I group). No statistical difference was noted in low- versus high-dose 131I group with regard to the efficacy in ablation of residual thyroid tissue (OR=0.78, 95%CI=0.58-1.06, P=0.11), incidence of dry eye (OR=0.77, 95%CI=0.53-1.12, P=0.18) and incidence of dry mouth (OR=0.69, 95%CI=0.47-1.01, P=0.06). The incidences of both gastrointestinal adverse reactions and neck pain in low-dose 131I group were lower than that in high-dose 131I group (OR=0.32, 95%CI=0.18-0.55, P<0.001; OR=0.49, 95%CI=0.31-0.78, P=0.003). Conclusion: In differentiated thyroid cancer, the two doses of 131I have similar efficacy in postoperative ablation of thyroid remnant, but the low-dose regimen has less adverse effects.