Objective: To evaluate the changes and the prognostic value of serum vascular endothelial growth factor (VEGF) in patients with differentiated thyroid cancer (DTC). Subjects and Methods: A total of 79 patients with DTC and 30 healthy individuals were divided into four groups: (1) a healthy control group (n = 30); (2) DTC without recurrence (n = 35; 23 papillary, 12 follicular); (3) DTC with local recurrence (n = 24; 15 papillary, 9 follicular), and (4) DTC with lung metastasis (n = 20; 13 papillary, 7 follicular). Serum VEGF and thyroglobulin levels were measured in all patients. Results: Serum levels of VEGF were significantly higher in the lung metastasis group than in the other three groups (p < 0.05). Serum thyroglobulin concentration positively correlated with VEGF expression (r = 0.8678, p < 0.001) in patients with thyroid cancer recurrence. Multivariate Cox regression analysis showed that clinical staging (OR = 1.851, 95% CI 1.04'3.47; p = 0.038), noncompliance with postoperative thyroxin replacement therapy (OR = 1.935, 95% CI 1.03'3.65; p = 0.042) and postoperative levels of thyroglobulin (OR = 1.892, 95% CI 1.01'3.56, p = 0.032) were independent predictors for thyroid cancer recurrence. Every additional 100 ng/l of serum VEGF levels increased the risk of thyroid cancer recurrence by 20.3%; but this did not reach statistical significance (OR = 1.203, 95% CI 0.95'1.52; p = 0.125). Conclusions: Serum VEGF increased in patients with recurrent thyroid cancer following surgical therapies. The predictive value of serum VEGF requires further investigation.