BACKGROUND: Professional guidelines, both in Europe and North America, recommend completion thyroidectomy (CT) after lobe resection, except in very low-risk-differentiated thyroid cancer patients (tumor less than 1 cm; unifocal micropapillary carcinoma). Radioiodine lobar ablation (RAILA), which avoids complications associated with re-surgery, is an alternative that has been recently explored in a few international centers. However, this approach is being criticized as there are no published data available on its long-term outcomes with respect to recurrence rate, disease-free survival, and mortality compared with standard of care. This study was designed to compare the long-term outcome of RAILA with that of remnant ablation after CT. METHODS: Prospectively collected data were analyzed retrospectively from the case records of patients treated in our thyroid clinic in the last 25 years. The records of all patients of RAILA (364) and CT (372) were critically studied. Successful ablation rate, cumulative dose needed for complete ablation, recurrence rate, and recurrence-free survival were estimated for each group. Comparison between the two groups was made using the SPSS 11.5 statistical program. RESULTS: Radioiodine ablation rate at first dose of RAILA and remnant ablation after CT were 73 and 93.5%, respectively (P=0.03). However, after the second dose of I-131, the former group achieved successful ablation in 92% of patients. After a median follow-up period of 5 years (range 1-23 years), seven patients developed recurrence in the CT group (1.88%) and 14 in the RAILA group (3.8%); this was not statistically significant (P=0.168). The Kaplan-Meier disease-free survival curves between the two groups were statistically not significant (P=0.08). No cause-specific mortality in either group has been observed till date. CONCLUSION: Radioiodine lobar ablation is a safe, simple, effective, and less expensive alternative to CT in patients with differentiated thyroid cancer with comparable long-term outcome in terms of recurrence rate and disease-free survival.