Thyroid nodules with indeterminate fine-needle aspiration cytology (FNA) represent a major challenge in clinical practice. We conducted a systematic review and meta-analysis evaluating the ability of hybrid imaging using fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) to appropriately select these nodules for surgery. PubMed, CENTRAL, Scopus, and Web of Science were searched until July 2019. Original articles reporting data on the performance of F-FDG PET/CT in thyroid nodules with indeterminate FNA were included. Summary operating points including 95% confidence interval values (95% CI) were estimated using a random-effects model. Out of 786 retrieved papers, eight studies evaluating 104 malignant and 327 benign thyroid nodules were included. The pooled positive and negative likelihood ratios (LR+ and LR-) and diagnostic odds ratio (DOR) of F-FDG PET/CT were 1.7 (95% CI: 1.4-2.0), 0.4 (95% CI: 0.2-0.7), and 3.5 (95% CI: 1.7-7.1), respectively. No heterogeneity was found for LR+ and DOR. In patients with thyroid nodules with indeterminate FNA, F-FDG PET/CT has a moderate ability to correctly discriminate malignant from benign lesions and could represent a reliable option to reduce unnecessary diagnostic surgeries. However, further studies using standardized criteria for interpretation are needed to confirm the reproducibility of these findings.