(1) Background-low-dose radioiodine ablation is an accepted strategy for the treatment of low- and intermediate-risk thyroid carcinomas, although there is no international consensus. The aim of this study is to describe the clinical experience with low-dose radioiodine ablation in patients with low- and intermediate-risk thyroid cancer compared to high-dose ablation. (2) Methods-174 patients with low- and intermediate-risk thyroid cancer, 90 treated with low-dose ablation and 84 treated with high-dose ablation, were included. The primary endpoint was response to treatment one year after ablation, defined by stimulated thyroglobulin, whole body scan and ultrasound imaging. (3) Results-an excellent response rate of 79.8% in the low-dose group and 85.7% in the high-dose group was observed (p = 0.049). Stimulated thyroglobulin at the moment of ablation (p = 0.032) and positive antithyroglobulin antibodies (p < 0.001) were independent predictive factors for nonexcellent response. Young age (p = 0.023), intermediate initial recurrence risk (p < 0.001) and low-dose ablation (p = 0.004) were independent predictive factors for recurrence. (4) Conclusion-low-dose ablation seemed to be less effective than high-dose ablation, especially in those patients with positive antithyroglobulin antibodies or higher stimulated thyroglobulin levels at the moment of ablation. Low dose was associated with higher recurrence rates, and lower age and intermediate initial recurrence risk were independent risk factors for recurrence in our sample.