ObjectiveWe sought to evaluate and compare the outcomes of different surgical protocols for papillary thyroid cancer (PTC) located in the isthmus in a retrospective intention-to-treat analysis.Patients and methodsThe data of 3,068 patients who received thyroidectomy due to thyroid cancer in our center were reviewed. Of these, 103 patients had a dominant carcinoma located in the isthmus. Various baseline and tumor characteristics and surgical outcomes were evaluated and compared with respect to the different surgical protocols (85 cases with total thyroidectomy and 18 cases with less-than-total thyroidectomy). Univariate and multivariate analyses were performed to identify resected patients who developed recurrence with isthmic PTC.ResultsThe postoperative complication rates were comparable between the two groups (17.6% versus 11.1%, P=0.500). Although the total thyroidectomy group showed a much higher rate (P=0.004) and number (P<0.001) of parathyroidectomies, long-term follow-up indicated that parathyroid autotransplantation did not significantly damage the function of the parathyroid (P>0.05). Tumor recurrence was observed in five patients, including two patients in the total thyroidectomy group and three patients in the less-than-total thyroidectomy group; the tumor recurrence rate in the total thyroidectomy group was significantly lower than that in the less-than-total thyroidectomy group (P=0.040). Univariate and multivariate analyses indicated less-than-total thyroidectomy as a risk factor for tumor recurrence in PTC cases with tumors located at the isthmus (hazard ratio: 1.870, 95% confidence interval: 1.320–2.218, P<0.001).ConclusionOur findings indicate that total thyroidectomy is an appropriate initial surgical protocol for isthmic PTC due to the lower recurrence rate, comparable postoperative complication rate, and parathyroid function recovery.