Objective: To compare the clinical efficacies between central compartment dissection and 131I ablation for papillary thyroid cancer (PTC) following total thyroidectomy. Methods: Three hundred and ninety patients with cN0 PTC treated within five and a half years in our hospital were selected and their clinical data were retrospectively analyzed. Patients underwent either total thyroidectomy plus central compartment dissection (group A) or total thyroidectomy plus 131I ablation (group B) or total thyroidectomy only (group C). Results: The differences in incidences of postoperative complications that included recurrent laryngeal nerve injury, superior laryngeal nerve injury and hypoparathyroidism between group of patients with central compartment dissection (group A) and group of patients without central compartment dissection (group B and C) showed no statistical significance (all P>0.05), and radiation injury associated with 131I therapy in group B was 51.5%. Comparisons in 5-year recurrence and metastasis among the three groups showed that the central compartment recurrence in group A was 0, which was significantly lower than that in group B (7.7%) or group C (13.8%) (both P<0.05). The incidences of lateral neck metastases and elevated serum thyroglobulin with no radiographic evidence presented an increase in ascending order in group A, B and C (1.5%, 6.2% and 9.2%; 3.1%, 7.7% and 15.4%, respectively), and the differences between group A and C had statistical significance (both P<0.05). The average length of hospital stay was longest with the highest hospitalization costs for group B, and the differences had statistical significance versus group A or group C (all P<0.05). Conclusion: Total thyroidectomy with central lymph node dissection for papillary thyroid cancer reduces the recurrence rate without an increased risk of complications. 131I treatment cannot completely replace lymph node dissection, and may also increase the associated complications, length of hospital stay and expenses of the patients.