Purpose: To evaluate the value of thyroglobulin doubling time (Tg-DT) in predicting 18F-FDG PET/CT findings and clinical outcomes in differentiated thyroid cancer (DTC) patients with high thyroglobulin (Tg) level and negative 131I whole-body scan (131I WBS). Results: The specificity and positive predictive value of Tg-DT for predicting 18F-FDG PET/CT findings were 93.94%, and 92.6%, respectively, while those for Tg levels were 78.79% and 83.53% (p < 0.001). This study revealed that stimulated Tg and Tg-DT can predict disease progression and survival in DTC patients. Age > 55, distant metastasis on 18F-FDG PET/CT, and Tg-DT ≤ 12 months were independent predictors of PFS. Distant metastasis and Tg-DT ≤ 12 months were independent prognostic factors for OS. Conclusion: Tg-DT is a valuable biomarker in predicting positive 18F-FDG PET/CT findings in DTC patients with high Tg level and negative 131I WBS. Along with distant metastases, Tg-DT ≤ 12 months is the only independent prognostic factor for PFS and OS.