The effects of low-activity versus high-activity radioiodine regimens in thyroid remnant ablation for patients with differentiated thyroid carcinoma (DTC) under recombinant human thyrotropin (rhTSH) stimulation have been widely quoted but there has been no systematic review of the evidence. We undertook a systematic review of randomized controlled trials to assess the effects of low-activity radioiodine in thyroid remnant ablation in patients with DTC under rhTSH stimulation compared with high-activity radioiodine. Studies were obtained from computerized searches of MEDLINE, EMBASE, and the Cochrane Library (all until September 2012). Randomized controlled trials were included. Altogether, 637 patients with DTC who participated in three trials for residual ablation were included. Overall, studies had a low risk of bias. We found no statistically significant differences between low-activity (1.11/1.85 GBq) and high-activity (3.7 GBq) radioiodine treatment aided by rhTSH in terms of successful ablation rates on the basis of diagnostic scans [odds ratio (OR) 0.85, 95% confidence interval (CI) 0.49-1.47, P=0.56], thyroglobulin levels (OR 0.66, 95% CI 0.38-1.15, P=0.14), and health-related quality of life (mean difference 0.07, 95% CI -0.96 to 1.09, P=0.9). In addition, the subgroup analysis of 1.11 versus 3.7 GBq (OR 0.83, 95% CI 0.46-1.49, P=0.53) and 1.85 versus 3.7 GBq (OR 1, 95% CI 0.23-4.35, P=1) also showed no significant differences. The lower activity of 1.11 GBq showed significant benefit in terms of reduction in adverse events including neck pain, radiation gastritis, and salivary dysfunction during and after ablation (OR 0.63, 95% CI 0.42-0.93, P=0.02). Limited data from three randomized controlled trials suggested that an rhTSH-aided low radioiodine activity level of as low as 1.115 GBq may be sufficient for thyroid remnant ablation when compared with 3.7 GBq, with fewer common adverse effects in patients with metastasis-free DTC. Further evidence is needed to confirm the effects of low-activity radioiodine for thyroid remnant ablation. Radioiodine treatment of 1.11 GBq showed significant benefit in terms of reduction in adverse events including neck pain, radiation gastritis, and salivary dysfunction during and after ablation (OR 0.63, 95% CI 0.42-0.93, P=0.02). rhTSH-aided low radioiodine activity levels of 1.11 and 1.85 GBq are sufficient for thyroid remnant ablation as compared with 3.7 GBq, with fewer common adverse effects in patients with metastasis-free DTC. A well-designed study that compares low-activity with high-activity radioiodine ablation is needed to fully understand the long-term adverse effects and relapse or metastases.