The surgical management of differentiated thyroid cancer remains controversial. Total thyroidectomy has been associated with higher rates of post-operative morbidity than more conservative surgery, but radioiodine ablation of residual thyroid tissue is considered to be particularly difficult after lobectomy. The purpose of this retrospective study was to assess the feasibility of 131I ablation after lobectomy, compared with total thyroidectomy, in patients who had undergone surgery for differentiated thyroid carcinoma. A retrospective analysis was performed of 225 post-surgical thyroid cancer patients treated with 3500 MBq 131I for the ablation of thyroid remnants. One hundred and sixty-five patients (73%) had previously undergone total thyroidectomy, whilst 60 patients (27%) had been treated by lobectomy. All patients underwent diagnostic scintigraphy, with 40 MBq 131I, 2 days prior to ablative therapy and at 3 months post-ablation. The median pre-ablative 131I neck uptake values were 3.3% and 20.1% in patients treated by total thyroidectomy and lobectomy, respectively (P < 0.001). Pre-ablation neck uptake correlated strongly with the whole-body 131I burden 2 days after 131I therapy (P < 0.001), and the biological half-life of the radioiodine was markedly longer after lobectomy than after total thyroidectomy. Ninety-eight per cent of patients treated by total thyroidectomy were successfully ablated by one 131I treatment, compared with 90% after lobectomy (P < 0.05). There were no significant differences in 131I neck uptake or serum thyroglobulin levels between the two patient groups at 3 months post-ablation. These data show that high rates of thyroid ablation can be achieved with a single fixed dose of 131I after thyroid lobectomy. The use of this surgical procedure may result in a longer period of patient isolation than that required after total thyroidectomy. However, the clear correlation between pre-ablation neck uptake and 131I burden at 2 days post-therapy enables effective treatment scheduling, so making lobectomy followed by 131I ablation a practical option for the management of differentiated thyroid cancer.